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                                                                    EXHIBIT 10.5

                                                                  EXECUTION COPY

                          REGISTRATION RIGHTS AGREEMENT

         This Registration Rights Agreement (this "Agreement") is entered into
as of July 31, 2003 by and among Alnylam Holding Co., a Delaware corporation
(the "Corporation"), and the persons and entities listed on Schedule A hereto
together with any persons or entities that become parties hereto pursuant to
Section 21 hereof (the "Investors").

         WHEREAS, on the date hereof, Alnylam Transitory Subsidiary, Inc., a
Delaware corporation, has been merged (the "Merger") with and into Alnylam
Pharmaceuticals, Inc., a Delaware corporation ("Alnylam"), the result of which
will be that Alnylam has become a wholly-owned subsidiary of the Corporation and
the Investors and Founders have received the same number and type of securities
of the Corporation as they formerly held in Alnylam;

         WHEREAS, in connection with the Merger, the Corporation and the
Investors are entering into this Agreement;

         WHEREAS, the Corporation, Alnylam, Ribopharma AG, a German stock
corporation ("Ribopharma") and the stockholders of Ribopharma have entered into
a Share Exchange Agreement, dated as of the date hereof (the "Share Exchange
Agreement"), upon the closing of which the stockholders of Ribopharma shall
contribute to the Corporation all of the shares of Ribopharma owned by such
stockholders in consideration for shares of the Corporation and cash, the result
of which will be that Ribopharma will become a wholly-owned subsidiary of the
Corporation;

         WHEREAS, subsequent to the closing of the Merger, the Corporation will
enter into a Series A and Series B Convertible Preferred Stock Purchase
Agreement, pursuant to which the Corporation will issue additional shares of its
Series A Convertible Preferred Stock, $.0001 par value per share (the "Series A
Preferred Stock"), and Series B Convertible Preferred Stock, $.0001 par value
per share (the "Series B Preferred Stock"), to the Investors and certain other
persons or entities (the "Financing");

         WHEREAS, it will be a condition to the closing of the Financing that
each investor in the Financing that is not already party to this Agreement shall
become party to this Agreement as an Investor hereunder;

         WHEREAS, in connection with certain license agreements to be entered
into by the Corporation, the Corporation expects to issue additional shares of
its Series B Preferred Stock to each of Garching Innovation GmbH, Massachusetts
Institute of Technology, Whitehead Institute for Biomedical Research,
Max-Planck-Gesellschaft zur Foerderung der Wissenschaften e.V and the University
of Massachusetts Medical School (each, an "Institutional Stockholder" and
collectively, the "Institutional Stockholders"); and

         WHEREAS, in connection with the issuance of such shares of Series B
Preferred Stock to the Institutional Stockholders, each Institutional
Stockholder receiving shares of Series B Preferred stock will become party to
this Agreement as an Investor hereunder.

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         NOW, THEREFORE, in consideration of the premises and mutual agreements
hereinafter set forth, and for other valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties hereto agree as
follows:

         SECTION 1. Definitions. As used in this Agreement, the following terms
shall have the following meanings:

                  (a)      The term "1934 Act" means the Securities Exchange Act
of 1934, as amended.

                  (b)      The term "Common Stock" means the Corporation's
Common Stock, $.0001 par value per share.

                  (c)      The term "Holder" means any holder of Registrable
Shares.

                  (d)      The terms "register," "registered," and
"registration" refer to a registration effected by preparing and filing a
registration statement in compliance with the Securities Act and the declaration
or ordering of effectiveness of such registration statement.

                  (e)      The term "Preferred Stock" means the Series A
Preferred Stock and the Series B Preferred Stock.

                  (f)      The term "Qualified IPO" means the closing of the
Corporation's first firm commitment underwritten public offering pursuant to an
effective registration statement under the Securities Act covering the offer and
sale of Common Stock for the account of the Corporation to the public at an
offering price per share (prior to underwriters' discounts and commissions) of
not less than $7.50 (as adjusted to reflect any stock dividends, distributions,
combinations, reclassifications or other like transactions effected by the
Corporation in respect of its Common Stock) and with gross proceeds to the
Corporation of not less than $25,000,000.

                  (g)      The term "Registrable Shares" means (1) the Common
Stock issuable upon conversion of the Preferred Stock, (2) any Common Stock
purchased by an Investor (or its permitted transferees) pursuant to Section 3 of
the Investor Rights Agreement of even date herewith by and among the Corporation
and the Investors (or Common Stock issuable with respect to other securities so
purchased), and (3) any Common Stock of the Corporation issued as a dividend or
other distribution with respect to, or in exchange or in replacement of, such
Preferred Stock or Common Stock; provided, that the Registrable Shares of any
Holder shall be deemed not to be Registrable Shares under this Agreement at any
time when the Corporation's Common Stock is publicly traded and all such
Registrable Shares can be sold within a 90-day period pursuant to Rule 144.

                  (h)      The term "Rule 144" means Rule 144 promulgated under
the Securities Act.

                  (i)      The term "SEC" means the Securities and Exchange
Commission.

                  (j)      The term "Securities Act" means the Securities Act of
1933, as amended.

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                  (k)      The term "Series A Preferred Stock" shall have the
meaning set forth in the recitals to this Agreement.

                  (l)      The term "Series B Preferred Stock" shall have the
meaning set forth in the recitals to this Agreement.

         In addition, for purposes of all calculations and notices under this
Agreement, and all other provisions of this Agreement where the context permits,
a holder of Preferred Stock shall be deemed the Holder of the Registrable Shares
issuable upon conversion thereof, and such Preferred Stock shall be deemed
outstanding Registrable Shares hereunder. Notwithstanding the foregoing, nothing
in this Agreement shall require the Corporation actually to register any shares
of Preferred Stock.

         SECTION 2. Request for Registration. If at any time after the earlier
to occur of (i) the fourth anniversary of the date of this Agreement and (ii)
the date twelve months after the Qualified IPO, the Corporation shall receive a
written request (specifying that it is being made pursuant to this Section 2)
from one or more Holders that hold, in aggregate, at least 33% of the then
outstanding Registrable Shares, that the Corporation file a registration
statement under the Securities Act, or a similar document pursuant to any other
statute then in effect corresponding to the Securities Act, covering the
registration of at least the lesser of (a) at least 25% of the then outstanding
Registrable Shares or (b) Registrable Shares the expected price to the public of
which equals or exceeds $5,000,000 (based on the market price or fair value on
the date of such request), then the Corporation shall promptly notify all other
Holders of such request and shall use its best efforts to cause all Registrable
Shares that Holders have requested be registered to be registered under the
Securities Act on Form S-1.

         Notwithstanding the foregoing, (i) the Corporation shall not be
obligated to effect a registration pursuant to this Section 2 during the period
starting with the date sixty (60) days prior to the Corporation's estimated date
of filing of, and ending on a date six (6) months following the effective date
of, a registration statement pertaining to an underwritten public offering of
securities for the account of the Corporation, provided that the Corporation is
actively employing in good faith its best efforts to cause such registration
statement to become effective and that the Corporation's estimate of the date of
filing such registration statement is made in good faith; (ii) the Corporation
shall not be obligated to effect a registration pursuant to this Section 2
within six (6) months after the effective date of a prior registration under
this Section 2; and (iii) if the Corporation shall furnish to the Holders a
certificate signed by the President of the Corporation stating that in the good
faith judgment of the Board of Directors it would be seriously detrimental to
the Corporation or its shareholders for a registration statement to be filed in
the near future, then the Corporation's obligation to use its best efforts to
file a registration statement shall be deferred for a period not to exceed 45
days.

         The Corporation shall not be obligated to effect more than two
registrations on behalf of the Holders pursuant to this Section 2.

         SECTION 3. Corporation Registration. If at any time the Corporation
proposes to register any of its Common Stock under the Securities Act in
connection with the public offering

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of such securities for its own account or for the accounts of shareholders other
than Holders, solely for cash on a form that would also permit the registration
of the Registrable Shares, the Corporation shall, each such time, promptly give
each Holder written notice of such determination. Upon the written request of
any Holder given within thirty (30) days after giving of any such notice by the
Corporation, the Corporation shall, subject to the limitations set forth in
Section 8, use its best efforts to cause to be registered under the Securities
Act all of the Registrable Shares that each such Holder has requested be
registered; provided, that the Corporation shall have the right to postpone or
withdraw any registration statement relating to an offering in which the Holders
are eligible to participate under this Section 3 without any liability or
obligation to the Holders under this Section 3.

         SECTION 4. Obligations of the Corporation. Whenever required under
Section 2, Section 3 or Section 11 to use its best efforts to effect the
registration of any Registrable Shares, the Corporation shall, as expeditiously
as reasonably possible:

                  (a)      Prepare and file with the SEC a registration
statement with respect to such Registrable Shares and use its best efforts to
cause such registration statement to become and remain effective until the
distribution thereof has been completed.

                  (b)      Prepare and file with the SEC such amendments and
supplements to such registration statement and the prospectus used in connection
with such registration statement as may be necessary to comply with the
provisions of the Securities Act with respect to the disposition of all
securities covered by such registration statement.

                  (c)      Furnish to the selling Holders such numbers of copies
of a prospectus, including a preliminary prospectus, in conformity with the
requirements of the Securities Act, and such other documents as they may
reasonably request in order to facilitate the disposition of such Registrable
Shares owned by them.

                  (d)      Use its best efforts to register and qualify the
securities covered by such registration statement under such other securities or
Blue Sky laws of such jurisdictions as shall be reasonably appropriate for the
distribution of the securities covered by the registration statement, provided
that the Corporation shall not be required in connection therewith or as a
condition thereto to qualify to do business or to file a general consent to
service of process in any such states or jurisdictions, and further provided
that (anything in this Agreement to the contrary notwithstanding with respect to
the bearing of expenses) if any jurisdiction in which the securities shall be
qualified shall require that expenses incurred in connection with the
qualification of the securities in that jurisdiction be borne by selling
shareholders, then such expenses shall be payable by selling shareholders pro
rata, to the extent required by such jurisdiction.

                  (e)      Provide a transfer agent for the Common Stock no
later than the effective date of the first registration of any Registrable
Shares.

                  (f)      Otherwise use its best efforts to comply with all
applicable rules and regulations of the SEC.

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                  (g)      Use its best efforts either (i) to cause all such
Registrable Shares to be listed on a national securities exchange (if such
securities are not already so listed) and on each additional national securities
exchange on which similar securities issued by the Corporation are then listed,
if the listing of such securities is then permitted under the rules of such
exchange, or (ii) to secure designation of all such Registrable Shares as a
Nasdaq "national market system security" within the meaning of Rule 11Aa2-1 of
the SEC or, failing that, to secure listing on Nasdaq for such Registrable
Shares and, without limiting the generality of the foregoing, to arrange for at
least two (2) market makers to register as such with respect to Registrable
Shares with the National Association of Securities Dealers.

                  (h)      Enter into such customary agreements (including an
underwriting agreement in customary form) and take such other actions as the
selling Holders of Registrable Shares shall reasonably request in order to
expedite or facilitate the disposition of such Registrable Shares.

                  (i)      Make available for inspection by any selling Holder
of Registrable Shares, by any underwriter participating in any disposition to be
effected pursuant to such registration statement and by any attorney, accountant
or other agent retained by any such selling Holder or any such underwriter, all
pertinent financial and other records and pertinent corporate documents and
properties of the Corporation, and cause all of the Corporation's officers,
directors and employees to supply all information reasonably requested by any
such selling Holder, underwriter, attorney, accountant or agent in connection
with such registration statement.

                  (j)      Use every reasonable effort to prevent the issuance
of any stop order suspending the effectiveness of such registration statement or
of any order preventing or suspending the use of any preliminary prospectus and,
if any such order is issued, to obtain the lifting thereof at the earliest
reasonable time.

                  (k)      Make such representations and warranties to the
selling Holders of Registrable Shares and the underwriters as are customarily
made by issuers to selling stockholders and underwriters, as the case may be, in
primary underwritten public offerings.

         SECTION 5. Furnish Information. It shall be a condition precedent to
the obligations of the Corporation to take any action pursuant to this Agreement
with respect to the registration of any Holder's Registrable Shares that such
Holder shall take such actions and furnish to the Corporation such information
regarding itself, the Registrable Shares held by it, and the intended method of
disposition of such securities, as the Corporation shall reasonably request and
as shall be required in connection with any registration, qualification or
compliance referred to in this agreement, including, without limitation (i) in
connection with an underwritten offering, enter into an appropriate underwriting
agreement containing terms and provisions then customary in agreements of that
nature, (ii) enter into such custody agreements, powers of attorney and related
documents at such time and on such terms and conditions as may then be
customarily required in connection with such offering and (iii) distribute the
Registrable Shares only in accordance with and in the manner of the distribution
contemplated by the applicable registration statement and prospectus. In
addition, the Holders shall promptly notify the Corporation of any request by
the

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Commission or any state securities commission or agency for additional
information or for such registration statement or prospectus to be amended or
supplemented.

         SECTION 6. Expenses of Demand Registration. All expenses incurred in
connection with any registration pursuant to Section 2 or Section 11 (excluding
underwriters' discounts and commissions), including, without limitation, all
registration and qualification fees, printers' and accounting fees, fees and
disbursements of counsel for the Corporation, and the reasonable fees and
disbursements of one special counsel for the selling Holders collectively, shall
be borne by the Corporation.

         SECTION 7. Corporation Registration Expenses. All expenses (excluding
underwriters' discounts and commissions) incurred in connection with any
registration pursuant to Section 3, including, without limitation, any
additional registration and qualification fees and any additional fees and
disbursements of counsel to the Corporation that result from the inclusion of
securities held by the selling Holders in such registration and the reasonable
fees and disbursements of one special counsel for the selling Holders
collectively, shall be borne by the Corporation.

         SECTION 8. Underwriting Requirements.

                  (a)      In connection with any offering under Section 3
involving an underwriting of shares being issued by the Corporation, the
Corporation shall not be required to include any Holder's Registrable Shares in
such underwriting unless such Holder accepts the terms of the underwriting as
agreed upon between the Corporation and the underwriters selected by it, and
then only in such quantity as will not, in the reasonable opinion of the
underwriters, jeopardize the success of the offering by the Corporation. If the
total amount of securities that all Holders request to be included in an
underwritten offering under Section 3 exceeds the amount of securities that the
underwriters reasonably believe compatible with the success of the offering, no
securities of any shareholder except (i) securities included in such
underwritten offering pursuant to the exercise of contractual demand
registration rights and (ii) Registrable Shares of Holders shall be included in
such offering unless all Registrable Shares which the Holders have requested to
be included are included, and the Corporation shall only be required to include
in the offering so many of the Registrable Shares of the Holders as the
underwriters reasonably believe will not jeopardize the success of the offering
(the Registrable Shares so included to be apportioned pro rata among the selling
Holders according to the total amount of Registrable Shares owned by such
selling Holders, or in such other proportions as shall mutually be agreed to by
such selling Holders).

                  (b)      With respect to any underwriting of shares to be
registered under Section 2 or Section 11, the selling Holders who initiate the
request for registration shall have the right to designate the managing
underwriter or underwriters, subject to the consent of the Corporation. In
connection with any underwritings of shares to be registered under Section 3,
the Corporation shall have the right to designate the managing underwriter or
underwriters. In any such case, such consent of the Corporation or the Holders
shall not be unreasonably withheld or delayed.

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         SECTION 9. Delay of Registration. No Holder shall have any right to
take any action to restrain, enjoin, or otherwise delay any registration as the
result of any controversy that might arise with respect to the interpretation or
implementation of this Agreement.

         SECTION 10. Indemnification. In the event any Registrable Shares are
included in a registration statement under this Agreement:

                  (a)      To the extent permitted by law, the Corporation will
indemnify and hold harmless each Holder requesting or joining in a registration,
any underwriter (as defined in the Securities Act) for it, and each person, if
any, who controls any such Holder or underwriter within the meaning of the
Securities Act, against any losses, claims, damages or liabilities, joint or
several, to which they may become subject under the Securities Act or otherwise,
insofar as such losses, claims, damages or liabilities (or actions in respect
thereof) arise out of or are based on (i) any untrue or alleged untrue statement
of any material fact contained in such registration statement, including,
without limitation, any preliminary prospectus or final prospectus contained
therein or any amendments or supplements thereto, (ii) the omission or alleged
omission to state therein a material fact required to be stated therein, or
necessary to make the statements therein not misleading or (iii) any violation
by the Corporation of any rule or regulation promulgated under the Securities
Act applicable to the Corporation and relating to action or inaction required of
the Corporation in connection with any such registration; and will promptly
reimburse each such Holder, underwriter, or controlling person for any legal or
other expenses reasonably incurred by them in connection with investigating or
defending any such loss, claim, damage, liability, or action, provided, however,
that the indemnity agreement contained in this Section 10(a) shall not apply to
amounts paid in settlement of any such loss, claim, damage, liability or action
if such settlement is effected without the consent of the Corporation (which
consent shall not be unreasonably withheld or delayed) nor shall the Corporation
be liable in any such case for any such loss, claim, damage, liability or action
to the extent that it (i) arises out of or is based upon an untrue statement or
alleged untrue statement or omission or alleged omission made in connection with
such registration statement, preliminary prospectus, final prospectus, or
amendments or supplements thereto, in reliance upon and in conformity with
written information furnished to the Corporation expressly for use in connection
with such registration by or on behalf of any such Holder, underwriter or
controlling person, (ii) is caused by the failure of a Holder to deliver a copy
of the final prospectus relating to such Registrable Shares, as then amended or
supplemented, in connection with a purchase, if the Corporation had previously
furnished copies thereof to such Holder or (iii) is caused by such Holder's
disposition of Registrable Shares during any period during which such Holder is
obligated to discontinue any disposition of Registrable Shares under Section 18.

                  (b)      To the extent permitted by law, each Holder
requesting or joining in a registration will indemnify and hold harmless the
Corporation, each of its directors, each of its officers who has signed the
registration statement, each person, if any, who controls the Corporation within
the meaning of the Securities Act, and any underwriter (within the meaning of
the Securities Act) for the Corporation against any losses, claims, damages or
liabilities to which the Corporation or any such director, officer, controlling
person or underwriter may become subject, under the Securities Act or otherwise,
insofar as such losses, claims, damages or liabilities (or actions in respect
thereto) arise out of or are based upon (i) any untrue statement or

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alleged untrue statement of any material fact contained in such registration
statement, including any preliminary prospectus or final prospectus contained
therein or any amendments or supplements thereto or (ii) the omission or alleged
omission to state therein a material fact required to be stated therein or
necessary to make the statements therein not misleading, in each case to the
extent, but only to the extent, that such untrue statement or alleged untrue
statement or omission or alleged omission was made in reliance upon and in
conformity with written information relating to and furnished to the Corporation
by such Holder expressly for use in connection with such registration; and will
promptly reimburse the Corporation or any such director, officer, controlling
person or underwriter for any legal or other expenses reasonably incurred by
them in connection with investigating or defending any such loss, claim, damage,
liability or action; provided, however, that the indemnity agreement contained
in this Section 10(b) shall not apply to amounts paid in settlement of any such
loss, claim, damage, liability or action if such settlement is effected without
the consent of such Holder (which consent shall not be unreasonably withheld or
delayed) and provided further that no Holder shall have any liability under this
Section 10(b) in excess of the net proceeds actually received by such Holder in
the relevant public offering.

                  (c)      Promptly after receipt by an indemnified party under
this Section 10 of notice of the commencement of any action, such indemnified
party will, if a claim in respect thereof is to be made against any indemnifying
party under this Section 10, notify the indemnifying party in writing of the
commencement thereof and the indemnifying party shall have the right to
participate in, and, to the extent the indemnifying party so desires, jointly
with any other indemnifying party similarly noticed, to assume the defense
thereof with counsel mutually satisfactory to the parties. The failure to notify
an indemnifying party promptly of the commencement of any such action, if
prejudicial to his ability to defend such action, shall relieve such
indemnifying party of any liability to the indemnified party under this Section
10, but the omission so to notify the indemnifying party will not relieve him of
any liability that he may have to any indemnified party otherwise than under
this Section 10.

                  (d)      If the indemnification provided for in this Section
10 is required by its terms but is for any reason held to be unavailable to or
otherwise insufficient to hold harmless an indemnified party under Section 10(a)
or Section 10(b) in respect of any losses, claims, damages, liabilities or
expenses referred to herein, then each applicable indemnifying party shall
contribute to the amount paid or payable by such indemnified party as a result
of any losses, claims, damages, liabilities or expenses referred to herein (i)
in such proportion as is appropriate to reflect the relative benefits received
by the Corporation and the selling Holders from the offering of securities or
(ii) if the allocation provided by clause (i) above is not permitted by
applicable law, in such proportion as is appropriate to reflect not only the
relative benefits referred to in clause (i) above but also the relative fault of
the Corporation and the selling Holders in connection with the statements or
omissions described in such Section 10(a) or Section 10(b) which resulted in
such losses, claims, damages, liabilities or expenses, as well as any other
relevant equitable considerations. The respective relative benefits received by
the Corporation and the selling Holders shall be deemed to be in the same
proportion as the total price paid to the Corporation and the selling Holders,
respectively, for the securities sold by them in the offering. The relative
fault of the Corporation and the selling Holders shall be determined by
reference to, among other things, whether the untrue or alleged untrue statement
of a material fact or the

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omission or alleged omission to state a material fact relates to information
supplied by the Corporation or the selling Holders and the parties' relative
intent, knowledge, access to information and opportunity to correct or prevent
such statement or omission. The amount paid or payable by a party as a result of
the losses, claims, damages, liabilities and expenses referred to above shall be
deemed to include, subject to the limitations set forth in this Section 10, any
legal or other fees or expenses reasonably incurred by such party in connection
with investigating or defending any action or claim. The provisions set forth in
Section 10(c) with respect to notice of commencement of any action shall apply
if a claim for contribution is to be made under this Section 10(d); provided,
however, that no additional notice shall be required with respect to any action
for which notice has been given under subsection Section 10(c) for purposes of
indemnification. The Corporation and the selling Holders agree that it would not
be just and equitable if contribution pursuant to this Section 10 were
determined solely by pro rata allocation or by any other method of allocation
which does not take account of the equitable considerations referred to in this
paragraph. Notwithstanding the provisions of this Section 10(d), no Holder shall
be required to contribute an amount in excess of the net proceeds actually
received by such Holder in the relevant public offering. No person guilty of
fraudulent misrepresentation (within the meaning of Section 11(f) of the
Securities Act) shall be entitled to contribution from any person who was not
guilty of such fraudulent misrepresentation.

                  (e)      Notwithstanding the foregoing, to the extent that the
provisions on indemnification contained in the underwriting agreements entered
into among the Holders, the Corporation and the underwriters in connection with
an underwritten public offering are in conflict with the foregoing provisions,
the provisions in the underwriting agreement shall be controlling as to the
Registrable Shares included in the public offering.

         SECTION 11. Registrations on Form S-3.

                  (a)      If (i) the Corporation shall receive a written
request (specifying that it is being made pursuant to this Section 11) from one
or more Holders that the Corporation file a registration statement on Form S-3
(or any successor form to Form S-3 regardless of its designation) for a public
offering of Registrable Shares the reasonably anticipated aggregate price to the
public of which would equal or exceed $3,000,000, and (ii) the Corporation is a
registrant entitled to use Form S-3 (or any successor form to Form S-3) to
register such shares, then the Corporation shall promptly notify all other
Holders of such request and shall use its best efforts to cause all Registrable
Shares that Holders have requested be registered to be registered on Form S-3
(or any successor form to Form S-3).

                  (b)      Notwithstanding the foregoing, (i) the Corporation
shall not be obligated to effect a registration pursuant to this Section 11
during the period starting with the date sixty (60) days prior to the
Corporation's estimated date of filing of, and ending on a date six (6) months
following the effective date of, a registration statement pertaining to an
underwritten public offering of securities for the account of the Corporation,
provided that the Corporation is actively employing in good faith its best
efforts to cause such registration statement to become effective and that the
Corporation's estimate of the date of filing such registration statement is made
in good faith; (ii) the Corporation shall not be obligated to effect a
registration pursuant to this Section 11 within six (6) months after the
effective date of a prior registration under this

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Section 11; and (iii) if the Corporation shall furnish to the Holders a
certificate signed by the President of the Corporation stating that in the good
faith judgment of the Board of Directors it would be seriously detrimental to
the Corporation or its shareholders for a registration statement to be filed in
the near future, then the Corporation's obligation to use its best efforts to
file a registration statement shall be deferred for a period not to exceed 45
days.

                  (c)      The Holders' rights to registration under this
Section 11 are in addition to, and not in lieu of, their rights to registration
under Section 2 and Section 3 of this Agreement.

         SECTION 12. Limitation on Corporation Offerings. The Corporation shall
not register securities for sale for its own account (or, except as permitted by
Section 14, any securities other than Registrable Shares) in any registration
requested pursuant to Section 2 or Section 11 unless permitted to do so by the
written consent of the Holders of a majority of the Registrable Shares as to
which registration has been requested.

         SECTION 13. Reports Under Securities Exchange Act of 1934. With a view
to making available to the Holders the benefits of Rule 144 and any other rule
or regulation of the SEC that may at any time permit a Holder to sell securities
of the Corporation to the public without registration, the Corporation agrees to
use its best efforts to:

                  (a)      make and keep public information available, as those
terms are understood and defined in Rule 144, at all times subsequent to 90 days
after the effective date of the first registration statement covering an
underwritten public offering filed by the Corporation;

                  (b)      file with the SEC in a timely manner all reports and
other documents, if any, required of the Corporation under the Securities Act
and the 1934 Act; and

                  (c)      furnish to any Holder forthwith upon request a
written statement by the Corporation that it has complied with the reporting
requirements of Rule 144 (at any time after 90 days after the effective date of
said first registration statement filed by the Corporation), and of the
Securities Act and the 1934 Act (at any time after it has become subject to such
reporting requirements), a copy of the most recent annual or quarterly report of
the Corporation, and such other reports and documents so filed by the
Corporation as may be reasonably requested in availing any such holder to take
advantage of any rule or regulation of the SEC permitting the selling of any
such securities without registration.

         SECTION 14. Limitations in Connection with Future Grants of
Registration Rights. Without the prior written consent of the Holders of at
least 66 2/3% in voting power of then outstanding Registrable Shares held by
Investors, the Corporation shall not grant rights to any person or entity: (a)
to cause the Corporation to register any of such person's or entity's securities
of the Corporation; (b) to include such person's or entity's securities of the
Corporation in any registration statement filed under Section 2 or Section 11
hereof; (c) to include such person's or entity's securities of the Corporation
in any registration statement described in Section 3 hereof, unless under the
terms of such agreement, such person or entity may include such securities in
any such registration only to the extent that the inclusion of his or its
securities will not reduce the amount of Registrable Shares of the Holders which
is included

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in such registration; or (d) otherwise to cause the registration of such
person's or entity's securities of the Corporation in any manner which are
superior to or pari passu with the registration rights granted herein to the
Holders. Notwithstanding the foregoing, the Corporation shall be permitted to
grant registration rights to investors in the Financing by making such investors
parties to this Agreement in the manner set forth in Section 21 hereof.

         SECTION 15. Transfer of Registration Rights. The registration rights
and obligations of any Holder (and of any permitted transferee of any Holder or
its permitted transferees) under this Agreement with respect to any Registrable
Shares may be transferred to any Affiliate of such Holder or such permitted
transferee, or to any transferee who acquires (otherwise than in a registered
public offering) at least five percent (5%) of the Registrable Shares held by
such Holder on the date hereof (or, if such transfer occurs after the closing of
the Financing, at least five percent (5%) of the Registrable Shares held by such
Holder immediately after the closing of the Financing) provided, however, that
(a) such rights and obligations may not be transferred to any entity whose
primary line of business is directly competitive with the primary line of
business of the Corporation, (b) the Corporation shall be given written notice
by the Holder at the time of any permitted transfer stating the name and address
of the transferee and identifying the securities with respect to which the
rights and obligations under this Agreement are being assigned and (c) the
transferee shall execute an agreement to be bound by the terms of this
agreement. For purposes of this Section 15, an "Affiliate" of any Holder (or any
transferee of any Holder) means any general or limited partner of any Holder (or
transferee) that is a partnership, or any person or entity that, directly or
indirectly, through one or more intermediaries, controls, or is controlled by,
or is under common control with, such Holder or transferee.

         SECTION 16. Mergers, Etc. The Corporation shall not, directly or
indirectly, enter into any merger, consolidation or reorganization in which the
Corporation shall not be the surviving corporation unless the proposed surviving
corporation shall, prior to such merger, consolidation or reorganization, agree
in writing to assume the obligations of the Corporation under this Agreement,
and for that purpose references hereunder to "Registrable Shares" shall be
deemed to be references to the securities which the Holders would be entitled to
receive in exchange for Registrable Shares under any such merger, consolidation
or reorganization; provided, however, that the provisions of this Agreement
shall not apply in the event of any merger, consolidation or reorganization in
which the Corporation is not the surviving corporation if the holders of
Registrable Shares are entitled to receive in exchange therefor (i) cash, or
(ii) securities of the acquiring corporation which may be immediately sold to
the public without registration under the Securities Act.

         SECTION 17. Stand-Off Agreement. Each Holder, if requested by the
Corporation and the managing underwriter of an offering by the Corporation of
Common Stock pursuant to a registration statement under the Securities Act,
shall agree not to sell publicly or otherwise transfer or dispose of any
Registrable Shares or other securities of the Corporation held by such Holder
for a specified period of time (not to exceed 180 days) immediately following
the effective date of such registration statement; provided, that:

                  (a)      such agreement shall apply only to the Qualified IPO;
and

                                       11

<PAGE>

                  (b)      all persons who hold shares of Common Stock, or
securities convertible into or exchangeable or exercisable for shares of Common
Stock, which in aggregate represent one percent (1%) or more of the shares of
Common Stock then outstanding (which 1% shall include all securities convertible
into or exchangeable or exercisable for shares of Common Stock, on an as
converted, exchanged or exercised basis) (any such person, a "1% Stockholder"),
and all officers and directors of the Corporation, enter into similar
agreements.

         Any discretionary waiver or termination of the restrictions of such
agreements (including this Agreement) by the Corporation or the managing
underwriter shall apply to all persons subject to such agreements on a pro rata
basis, based upon the number of shares held by such persons, except for
discretionary waivers based on financial hardship, not to exceed $250,000 worth
of securities per individual or $500,000 in the aggregate (in each case based on
the market price or fair value on the date such waiver is granted), that are
granted to officers, directors or 1% Stockholders.

         SECTION 18. Future Events. The Corporation will notify each Holder
participating in a registration of the occurrence of any of the following events
of which the Corporation is actually aware, and when so notified, each Holder
will immediately discontinue any disposition of Registrable Shares until
notified by the Corporation that such event is no longer applicable:

                  (a)      the issuance by the Commission or any state
securities commission or agency of any stop order suspending the effectiveness
of the registration statement or the initiation of any proceedings for that
purpose (in which case the Corporation will make reasonable efforts to obtain
the withdrawal of any such order or the cessation of any such proceedings); or

                  (b)      the existence of any fact which makes untrue any
material statement made in the registration statement or prospectus or any
document incorporated therein by reference or which requires the making of any
changes in the registration statement or prospectus or any document incorporated
therein by reference in order to make the statements therein not misleading (in
which case the Corporation will make reasonable efforts to amend the applicable
document to correct the deficiency).

         SECTION 19. Notices. All notices, requests, consents and other
communications hereunder ("Notices") to any party shall be contained in a
written instrument addressed to such party at the address set forth below or
such other address as may hereafter be designated in writing by the addressee to
the addressor listing all parties and shall be deemed given (a) when delivered
in person or duly sent by fax showing confirmation of receipt, (b) three days
after being duly sent by first class mail postage prepaid (other than in the
case of Notices to or from any non-U.S. resident, which Notices must be sent in
the manner specified in clause (a) or (c)), or (c) two days after being duly
sent by DHL, Federal Express or other recognized express international courier
service:

                                       12

<PAGE>

                    if to the Corporation, to:

                    Alnylam Holding Co.
                    c/o John Conley
                    790 Memorial Drive, Suite 202
                    Cambridge, MA  02139

         if to the Investors, to their respective addresses as set forth on
Schedule A of this Agreement.

         SECTION 20. Miscellaneous.

                  (a)      This Agreement states the entire agreement of the
parties concerning the subject matter hereof, and supersedes all prior
agreements, written or oral, between or among them concerning such subject
matter.

                  (b)      This Agreement may be amended, and compliance with
any provision of this Agreement may be omitted or waived, only by the written
agreement of the Corporation and the Holders of at least 66 2/3% in voting power
of the then outstanding Registrable Shares.

                  (c)      This Agreement shall be governed by, and construed
and enforced in accordance with, the substantive laws of the Commonwealth of
Massachusetts, without regard to its principles of conflicts of laws.

                  (d)      This Agreement may be executed in any number of
counterparts, each such counterpart shall be deemed to be an original
instrument, and all such counterparts together shall constitute but one
agreement. Any such counterpart may contain one or more signature pages. This
Agreement may be executed by facsimile signature pages.

                  (e)      This Agreement shall terminate upon the three-year
anniversary of the Qualified IPO.

         SECTION 21. Accession. Each person or entity that purchases shares of
Series A Preferred Stock or Series B Preferred Stock that is not already party
to this Agreement shall automatically become a party to this Agreement as an
Investor by executing and delivering to the Corporation a counterpart signature
page in the form of Exhibit A hereto, and shall thereupon be deemed an
"Investor" for all purposes of this Agreement. Upon the execution and delivery
to the Corporation of any such counterpart signature page, Schedule A shall be
modified to reflect the addition of such new Investor.

                  [Remainder of page intentionally left blank.]

                                       13

<PAGE>

         IN WITNESS WHEREOF, the parties have executed this Registration Rights
Agreement as a contract under seal as of the date first written above.

                              ALNYLAM HOLDING CO.

                              By: /s/ John Maraganore
                                 ---------------------------------------------
                              Name: John Maraganore
                              Title:  President and Chief Executive Officer

                              INVESTORS

                              POLARIS VENTURE PARTNERS III, L.P.

                              By: Polaris Venture Management Co. III, L.L.C.
                                  Its General Partner

                              By: /s/ William E. Bilodeau
                                 ---------------------------------------------
                              Name: William E. Bilodeau
                              Title: Attorney-in-fact

                              POLARIS VENTURE PARTNERS
                              ENTREPRENEURS' FUND III, L.P.

                              By: Polaris Venture Management Co. III, L.L.C.
                                  Its General Partner

                              By: /s/ William E. Bilodeau
                                 ---------------------------------------------
                              Name: William E. Bilodeau
                              Title: Attorney-in-fact

<PAGE>

                              POLARIS VENTURE PARTNERS FOUNDERS' FUND III, L.P.

                              By: Polaris Venture Management Co. III, L.L.C.
                                  Its General Partner

                              By:  /s/ William E. Bilodeau
                                 ---------------------------------------------
                              Name: William E. Bilodeau
                              Title: Attorney-in-fact

                              CHP II, L.P.

                              By: CHP II Management, LLC,
                              Its: General Partner

                              By:  /s/ John K. Clarke
                                 ---------------------------------------------
                              Name: John K. Clarke
                              Title: Managing Member

                              ATLAS VENTURE FUND V, L.P.
                              ATLAS VENTURE PARALLEL FUND V-A, C.V.
                              ATLAS VENTURE PARALLEL FUND V-B, C.V.
                              ATLAS VENTURE ENTREPRENEURS' FUND V, L.P.

                              By: Atlas Venture Associates V, L.P.
                              Its: General Partner

                              By: Atlas Venture Associates V, Inc.
                              Its: General Partner

                              By:  Illegible
                                 ---------------------------------------------
                              Title: Vice President

<PAGE>

                              ATLAS VENTURE FUND VI, L.P.
                              ATLAS VENTURE ENTREPRENEURS' FUND VI, L.P.

                              By: Atlas Venture Associates VI, L.P.
                              Its: General Partner

                              By: Atlas Venture Associates VI, Inc.
                              Its: General Partner

                              By:  Illegible
                                ----------------------------------------------
                              Title: Vice President

                              ATLAS VENTURE FUND VI GmbH & Co. KG

                              By: Atlas Venture Associates VI, L.P.
                              Its: Managing General Partner

                              By: Atlas Venture Associates VI, Inc.
                              Its: General Partner

                              By:  Illegible
                                 ---------------------------------------------
                              Title: Vice President

                              ARCH VENTURE FUND V, L.P.

                              By: ARCH Venture Partners V, L.P.
                              Its: General Partner

                              By: ARCH Venture Partners V, LLC
                              Its: General Partner

                              By:  Illegible
                                 ---------------------------------------------
                              Title: Managing Director

<PAGE>

                              ARCH ENTREPRENEURS FUND, L.P.

                              By: ARCH Venture Partners V, L.P.
                              Its: General Partner

                              By: ARCH Venture Partners V, LLC
                              Its: General Partner

                              By:  Illegible
                                 ---------------------------------------------
                              Title: Managing Director

                              CAMBRIDGE SCIENCE EQUITIES, LLC, a
                              Delaware limited liability company

                              By: ALEXANDRIA REAL ESTATE EQUITIES,
                                  INC., a Maryland corporation, managing
                                  member

                              By:  /s/ Joel S. Marcus
                                 ---------------------------------------------
                                 Chief Executive Officer

                                   /s/ Phillip A. Sharp
                              ------------------------------------------------
                              Phillip A. Sharp
                                   /s/ Paul Schimmel
                              ------------------------------------------------
                              Paul Schimmel
                                   /s/ John G. Conley
                              ------------------------------------------------
                              John G. Conley

<PAGE>


                               ALNYLAM HOLDING CO.

                          REGISTRATION RIGHTS AGREEMENT

                       ADDITIONAL INVESTOR SIGNATURE PAGE

         By executing this page in the space provided, the undersigned hereby
agrees (i) that it is an "Investor" as defined in the Registration Rights
Agreement dated as of July 31, 2003, by and among Alnylam Holding Co. and the
parties named therein (the "Registration Rights Agreement"), (ii) that it is a
party to the Registration Rights Agreement for all purposes and (iii) that it is
bound by all terms and conditions of the Registration Rights Agreement.

         EXECUTED this 31st day of July, 2003.

                                         ABINGWORTH BIOVENTURES III A L.P.,
                                         ABINGWORTH BIOVENTURES III B L.P.,
                                         ABINGWORTH BIOVENTURES III C L.P. AND
                                         ABINGWORTH BIOVENTURES III
                                         EXECUTIVES L.P. acting through their
                                         manager
                                           ABINGWORTH MANAGEMENT LIMITED
                                        --------------------------------------
                                        (print name)

                                        By:   illegible
                                           -----------------------------------

                                        Title:  Director/Company Secretary
                                              --------------------------------


<PAGE>
                                                                       Exhibit A

                               ALNYLAM HOLDING CO.

                          REGISTRATION RIGHTS AGREEMENT

                       ADDITIONAL INVESTOR SIGNATURE PAGE

         By executing this page in the space provided, the undersigned hereby
agrees (i) that it is an "Investor" as defined in the Registration Rights
Agreement dated as of July   , 2003, by and among Alnylam Holding Co. and the
parties named therein (the "Registration Rights Agreement"), (ii) that it is a
party to the Registration Rights Agreement for all purposes and (iii) that it is
bound by all terms and conditions of the Registration Rights Agreement.

         EXECUTED this ____ day of _______, 2003.

                                        --------------------------------------
                                        (print name)

                                        By:
                                           -----------------------------------

                                        Title:
                                              --------------------------------

<PAGE>

                                   Schedule A

                                    Investors

Polaris Venture Partners III, L.P.
1000 Winter Street
Suite 3350
Waltham, MA 02451-1215
Fax: (781) 290-0880

Polaris Venture Partners Entrepreneurs' Fund III, L.P.
1000 Winter Street
Suite 3350
Waltham, MA 02451-1215
Fax: (781) 290-0880

Polaris Venture Partners Founders' Fund III, L.P.
1000 Winter Street
Suite 3350
Waltham, MA 02451-1215
Fax: (781) 290-0880

CHP II, L.P.
c/o Cardinal Partners
221 Nassau Street
Princeton, NJ 08542

Atlas Venture Fund V, L.P
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

Atlas Venture Parallel Fund V-A, C.V.
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

Atlas Venture Parallel Fund V-B, C.V.
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

<PAGE>

Atlas Venture Entrepreneurs' Fund V, L.P.
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

Atlas Venture Fund VI, L.P.
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

Atlas Venture Entrepreneurs' Fund VI, L.P.
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

Atlas Venture Fund VI GmbH & Co. KG
890 Winter Street
Suite 320
Waltham, MA 02451
Fax:  (781) 622-1701

ARCH Venture Fund V, L.P.
8725 W. Higgins Road
Suite 290
Chicago, IL 60631
Fax:  (773) 380-6606

ARCH V Entrepreneurs Fund, L.P.
8725 W. Higgins Road
Suite 290
Chicago, IL 60631
Fax:  (773) 380-6606

Cambridge Science Equities, LLC
c/o Alexandria Real Estate Equities, Inc.
135 N. Los Robles Avenue
Suite 250
Pasadena, CA 91101

Paul R. Schimmel
9822 La Jolla Farms Road
La Jolla, CA 92037

<PAGE>

Phillip A. Sharp
Center for Cancer Research
Room E17-529
Massachusetts Institute of Technology
Cambridge, MA 02139-4307
(For courier service, add: 40 Ames Street)

John Conley
40 Hosmer Road
Concord, MA  01742
<PAGE>

                               FIRST AMENDMENT TO
                          REGISTRATION RIGHTS AGREEMENT

      This First Amendment to the Registration Rights Agreement (the
"AMENDMENT") is made as of October 9, 2003 by and among Alnylam Holding Co., a
Delaware corporation (the "CORPORATION"), and the Holders, as defined in the
Registration Rights Agreement dated as of July 31, 2003 by and among the
Corporation and the persons and entities listed on Schedule A thereto (the
"RIGHTS AGREEMENT").

      WHEREAS, the Corporation proposes to issue and sell up to 504,825 shares
of its Series C Convertible Preferred Stock, $.0001 par value per share,
pursuant to and on the terms reflected in that certain Series C Convertible
Preferred Stock Purchase Agreement dated as of the date hereof, by and among the
Corporation and the entities listed on the Schedule of Investors attached
thereto and the Corporation and the Holders wish to add such shares of Series C
Preferred Stock to the provisions of the Rights Agreement; and

      WHEREAS, in accordance with Section 20(b) of the Rights Agreement, by
executing and delivering this Amendment, the Corporation and the Holders of at
least 66 2/3% in voting power of the outstanding Registrable Shares (as defined
in the Rights Agreement) have approved this Amendment.

      NOW, THEREFORE, in consideration of the premises and the mutual covenants
contained in this Amendment and for other good and valuable consideration, the
receipt and sufficiency of which are hereby acknowledged, the parties hereto
agree as follows:

      1.    Certain Defined Terms. All capitalized terms used herein and not
defined herein shall have the meanings ascribed to such terms in the Rights
Agreement.

      2.    Amendment of Rights Agreement.

      (i)   The Rights Agreement is hereby amended by deleting Section 1(e) in
its entirety and by substituting in lieu thereof the following Section 1(e):

            "(e)  The term "Preferred Stock" means the Series A Preferred Stock,
      the Series B Preferred Stock and the Series C Preferred Stock."

      (ii)  The Rights Agreement is hereby further amended by adding the
following Section 1(m):

            "(m)  The term "Series C Preferred Stock" means the Corporation's
      Series C Convertible Preferred Stock, $.0001 par value per share."
<PAGE>
      (iii) Except as amended hereby, all of the terms and conditions of the
Rights Agreement shall remain in full force and effect.

      3.    Counterparts. This Amendment may be executed in one or more
counterparts, each of which shall be deemed an original, but all of which
together shall constitute one and the same instrument.

                   REMAINDER OF PAGE INTENTIONALLY LEFT BLANK


                                      -2-
<PAGE>
      IN WITNESS WHEREOF, the undersigned have executed this Amendment as of the
date first above written.

CORPORATION:

ALNYLAM HOLDING CO.



By:  /s/ John G. Conley
    --------------------------------
Name: John G. Conley
Title: CFO

                                      -3-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



                                          Abingworth Management Ltd*
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

                                          By:    /s/ John Berriman
------------------------------------           ------------------------------
Signature                                 Name:  John Berriman
                                          Title:  Director

* Acting in its capacity as Manager of Abingworth Bioventures III A, B, C and
Exes LPs.


                                      -4-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



                                          Arch Ventures Fund V, L.P.
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

                                          By:   /s/  Karen Kerr
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:  Managing Director


                                      -5-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



                                          Arch V. Entrepreneurs Fund, L.P.
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

                                          By:   /s/  Karen Kerr
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:  Managing Director


                                      -6-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



                                          *
------------------------------------       ----------------------------------
Printed Name                              Name of Entity

                                          By:   /s/ illegible
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:

                                          * Atlas Venture Fund VI GmbH & Co. KG
                                          By:  Atlas Venture Associates VI, L.P.
                                               its managing limited partner
                                          By:  Atlas Venture Associates VI, Inc.
                                               its general partner


                                          * ATLAS VENTURE FUND VI, L.P.
                                          By:  Atlas Venture Associates VI, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates VI, Inc.
                                               its general partner


                                          * ATLAS VENTURE ENTREPRENEURS'
                                          FUND VI, L.P.
                                          By:  Atlas Venture Associates VI, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates VI, Inc.
                                               its general partner


                                          * ATLAS VENTURE FUND V, L.P.
                                          By:  Atlas Venture Associates V, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates V, Inc.
                                               its general partner


                                      -7-
<PAGE>
                                          * ATLAS VENTURE PARALLEL FUND
                                          V-A, C.V.
                                          By:  Atlas Venture Associates V, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates V, Inc.
                                               its general partner


                                          * ATLAS VENTURE ENTREPRENEURS'
                                          FUND V, L.P.
                                          By:  Atlas Venture Associates V, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates V, L.P.
                                               its general partner


                                          * ATLAS VENTURE PARALLEL FUND
                                          V-B, C.V.
                                          By:  Atlas Venture Associates V, L.P.
                                               its general partner
                                          By:  Atlas Venture Associates V, Inc.
                                               its general partner


                                      -8-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:

                                          CHP II, L.P.
                                          -----------------------------------
                                          Name of Entity

                                          By:  CHP II Management, LLC
------------------------------------           Its General Partner
Printed Name



                                          By:   /s/ John K. Clarke
------------------------------------          -------------------------------
Signature                                 Name:  John K. Clarke
                                          Title:  Managing Member


                                      -9-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:

                                          POLARIS VENTURE PARTNERS III, L.P.

                                          By:  Polaris Venture Management Co.
------------------------------------           III, L.L.C., Its General Partner
Printed Name



                                          By:   /s/ William E. Bilodeau
------------------------------------          -------------------------------
Signature                                 Name:  William E. Bilodeau
                                          Title:  Attorney-in-fact


                                      -10-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:

                                          POLARIS VENTURE PARTNERS
                                          ENTREPRENEURS' FUND III, L.P.

                                          By:  Polaris Venture Management Co.
------------------------------------           III, L.L.C., Its General Partner
Printed Name



                                          By:   /s/  William E. Bilodeau
------------------------------------          -------------------------------
Signature                                 Name:  William E. Bilodeau
                                          Title:  Attorney-in-fact


                                      -11-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:

                                          POLARIS VENTURE PARTNERS
                                          FOUNDERS' FUND III, L.P.

                                          By:  Polaris Venture Management Co.
------------------------------------           III, L.L.C., Its General Partner
Printed Name



                                          By:   /s/ Willliam E. Bilodeau
------------------------------------          -------------------------------
Signature                                 Name:  William E. Bilodeau
                                          Title:  Attorney-in-fact


                                      -12-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



David Bartel
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/  David Bartel                         By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -13-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



John G. Conley
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/  John G. Conley                       By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -14-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Kreutzer
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Kreutzer                              By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -15-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Stefan Limmer
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Stefan Limmer                         By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -16-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Paul Schimmel
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Paul Schimmel                         By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -17-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Phillip A. Sharp
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Phillip A. Sharp                      By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -18-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Thomas Tuschl
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Thomas Tuschl                         By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -19-
<PAGE>
               [First Amendment to Registration Rights Agreement,
                           Signature Page, CONTINUED]



HOLDERS:

FOR INDIVIDUALS:                          FOR ENTITIES:



Phillip Zamore
------------------------------------      -----------------------------------
Printed Name                              Name of Entity

/s/ Phillip Zamore                        By:
------------------------------------          -------------------------------
Signature                                 Name:
                                          Title:


                                      -20-

<PAGE>


                                SECOND AMENDMENT
                                       TO
                          REGISTRATION RIGHTS AGREEMENT

       Pursuant to a Consent, Waiver and Amendment Agreement, dated February 26,
2004, the Registration Rights Agreement, dated as of July 31, 2003 and amended
on October 9, 2003, by and among Alnylam Holding Co., a Delaware corporation
(the "Corporation"), and the Investors listed on Schedule A thereto (the
"Agreement") was amended as follows

         1.       The Agreement is amended by deleting Section 1(f) thereof in
                  its entirety and replacing it with the following:

                  "(f) The term "Qualified IPO" means the closing of the
                  Corporation's first firm commitment underwritten public
                  offering pursuant to an effective registration statement under
                  the Securities Act covering the offer and sale of Common Stock
                  for the account of the Corporation to the public with gross
                  proceeds to the Corporation of not less than $25,000,000."

         2.       Except as amended hereby, the Agreement shall remain in full
                  force and effect, and that, from and after the date of this
                  Amendment, all references in the Agreement to "the Agreement"
                  or "this Agreement" or similar terms shall be deemed to be
                  references to the Agreement as amended hereby.

         3.       This Amendment shall be governed by, and construed and
                  enforced in accordance with, the substantive laws of the
                  Commonwealth of Massachusetts, without regard to its
                  principles of conflicts of laws.

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