<PAGE>

                                                                   EXHIBIT 10.12

                             UNCONDITIONAL GUARANTY

         For and in consideration of certain loans by SILICON VALLEY BANK, a
California-chartered bank, with its principal place of business at 3003 Tasman
Drive, Santa Clara, California 95054 and with a loan production office located
at One Newton Executive Park, Suite 200,2221 Washington Street, Newton,
Massachusetts 02462, doing business under the name "Silicon Valley East"
("Bank") to ALNYLAM PHARMACEUTICALS, INC., a Delaware corporation (hereinafter,
the "Borrower"), which loans were made pursuant to a certain Loan and Security
Agreement between Borrower and Bank dated December 18, 2002, as may be amended
from time to time (hereinafter, the "Agreement"), the undersigned guarantor
Alnylam Holding Co., a Delaware corporation with its principal office at
Cambridge, MA ("Guarantor"), hereby unconditionally and irrevocably guarantees
the prompt and complete payment of all amounts that Borrower owes to Bank and
performance by Borrower of the Agreement, as may be amended from time to time
(the "Agreement"), in strict accordance with their respective terms.

         1.       If Borrower does not perform its obligations under the
Agreement Guarantor will immediately pay all amounts due (including, without
limitation, all principal, interest, and fees) and satisfy all Borrower's
obligations under the Agreement.

         2.       These obligations are independent of Borrower's obligations
and separate actions may be brought against Guarantor (whether action is brought
against Borrower or whether Borrower is joined in the action). Guarantor's
liability is not contingent on the genuineness or enforceability of the
Agreement.

         3.       Bank may, without notice to Guarantor and without affecting
Guarantor's obligations under this Guaranty: (a) renew, extend, or otherwise
change the terms of the Agreement; (b) take security for the payment of this
Guaranty or the Agreement; (c) exchange, enforce, waive and release any
security; and (d) apply the security and direct its sale as Bank, in its
discretion, chooses.

         4.       Guarantor waives:

                  (a)      Any right to require Bank to: (i) proceed against
         Borrower or any other person; (ii) proceed against or exhaust any
         security; or (iii) pursue any other remedy. Bank may exercise or not
         exercise any right or remedy it has against Borrower or any security it
         holds (including the right to foreclose by judicial or non-judicial
         sale) without affecting Guarantor's liability.

                  (b)      Any defenses from disability or other defense of
         Borrower or from the cessation of Borrowers liabilities.

                  (c)      Any setoff, defense or counterclaim against Bank.

                  (d)      Any defense from the absence, impairment or loss of
         any right of reimbursement or subrogation or any other rights against
         Borrower. Until Borrower's obligations to Bank have been paid,
         Guarantor has no right of subrogation or reimbursement or subrogation
         or other rights against Borrower.

                  (e)      Any right to enforce any remedy that Bank has against
         Borrower.

                  (f)      Any rights to participate in any security held by
         Bank.

                  (g)      Any demands for performance, notices of
         nonperformance or of new or additional indebtness. Gurantor is
         responsible for being and keeping itself informed of Borrower's
         financial

                                       1
<PAGE>

         condition. Unless Guarantor requests particular information, Bank has
         no duty to provide information to Guarantor.

         5.       Guarantor acknowledges that, to the extent Guarantor has or
may have rights of subrogation or reimbursement against Borrower for claims
arising out of this Guaranty, those rights may be impaired or destroyed if Bank
elects to proceed against any real property security of Borrower by non-judicial
foreclosure. That impairment or destruction could, under certain judicial cases
and based on equitable principles of estoppel, give rise to a defense by
Guarantor against its obligations under this Guaranty. Guarantor waives that
defense and any others arising from Bank's election to pursue non-judicial
foreclosure.

         6.       If Borrower becomes insolvent or is adjudicated bankrupt or
files a petition for reorganization or similar relief under the United States
Bankruptcy Code, or if a petition is filed against Borrower and/or any
obligation under the Agreement is terminated or rejected, or any obligation of
Borrower is modified or if Borrower's obligations are avoided Guarantor's
liability will not be affected and its liability will continue. If Bank must
return any payment because of the insolvency, bankruptcy or reorganization of
Borrower, Guarantor or any other guarantor, this Guaranty will remain effective
or be reinstated.

         7.       Guarantor subordinates any indebtedness of Borrower it holds
to Bank; and Guarantor will collect, enforce and receive payments as Bank's
trustee and will pay Bank those payments without reducing or affecting its
liability under this Guaranty.

         8.       Guarantor will pay Bank's reasonable attorneys' fees and other
costs and expenses incurred enforcing this Guaranty. This Guaranty may not be
waived, revoked or amended without Bank's prior written consent. If any
provision of this Guaranty is unenforceable, all other provisions remain
effective. This Guaranty represents the entire agreement among the parties about
this guaranty. No prior dealings, no usage of trade, and no parol or extrinsic
evidence may supplement or vary this Guaranty. Bank may assign this Guaranty.
This Guaranty benefits Bank, its successors and assigns. This Guaranty is in
addition to any other guaranties Bank obtains.

         9.       Guarantor represents and warrants that (i) it has taken all
action necessary to authorize execute, deliver and perform this Guaranty; (ii)
execution, delivery and performance of this Guaranty do not conflict with any
organizational documents or agreements to which it is a party; and (iii) this
Guaranty is a valid and binding obligation, enforceable against Guarantor
according to its terms.

         10.      Guarantor will do all of the following:

                  (a)      Maintain its corporate existence, remain in good
         standing in Delaware, and continue to qualify in each jurisdiction in
         which the failure to qualify could have a material adverse effect on
         the financial condition, operations or business. Maintain all licenses,
         approvals, and agreements, the loss of which could have a material
         adverse effect on its financial condition, operations or business.

                  (b)      Comply with all statutes and regulations if
         non-compliance could adversely affect its financial condition,
         operations or business.

                  (c)      Execute other instruments and take action Bank
         reasonably requests to effect the purposes of this Agreement.

         11.      Guarantor hereby grants to Bank, a lien, security interest and
right of setoff as security for all obligations to Bank, whether now existing or
hereafter arising upon and against all deposits, credits, collateral and
property, now or hereafter in the possession, custody, safekeeping or control of
Bank or any entity under the control of Bank (including a Bank subsidiary) or in
transit to any of them. At any time after

                                       2
<PAGE>

the occurrence and during the continuance of an Event of Default (as defined in
the Agreement), without demand or prior notice (but with prompt subsequent
notice), Bank may set off the same or any part thereof and apply the same to any
liability or obligation of Guarantor even though unmatured and regardless of the
adequacy of any other collateral securing the loan. ANY AND ALL RIGHTS TO
REQUIRE BANK TO EXERCISE ITS RIGHTS OR REMEDIES WITH RESPECT TO ANY OTHER
COLLATERAL WHICH SECURES THE LOAN, PRIOR TO EXERCISING ITS RIGHT OF SETOFF WITH
RESPECT TO SUCH DEPOSITS, CREDITS OR OTHER PROPERTY OF THE GUARANTOR, ARE HEREBY
KNOWINGLY, VOLUNTARILY AND IRREVOCABLY WAIVED.

         12.      Massachusetts law governs this Guaranty without regard to
principles of conflicts of law. Guarantor and Bank each submit to the exclusive
jurisdiction of the State and Federal courts in Massachusetts; provided,
however, that if for any reason Bank cannot avail itself of such courts in the
Commonwealth of Massachusetts, Guarantor accepts jurisdiction of the courts and
venue in Santa Clara County, California. NOTWITHSTANDING THE FOREGOING, THE BANK
SHALL HAVE THE RIGHT TO BRING ANY ACTION OR PROCEEDING AGAINST THE GUARANTOR OR
ITS PROPERTY IN THE COURTS OF ANY OTHER JURISDICTION WHICH THE BANK DEEMS
NECESSARY OR APPROPRIATE IN ORDER TO REALIZE ON THE COLLATERAL OR TO OTHERWISE
ENFORCE THE BANK'S RIGHTS AGAINST THE GUARANTOR OR ITS PROPERTY. GUARANTOR AND
BANK EACH WAIVE THEIR RIGHT TO A JURY TRIAL OF ANY CLAIM OR CAUSE OF ACTION
ARISING OUT OF OR BASED UPON THIS AGREEMENT, THE LOAN DOCUMENTS OR ANY
CONTEMPLATED TRANSACTION, INCLUDING CONTRACT, TORT, BREACH OF DUTY AND ALL OTHER
CLAIMS. THIS WAIVER IS A MATERIAL INDUCEMENT FOR BOTH PARTIES TO ENTER INTO THIS
AGREEMENT. EACH PARTY HAS REVIEWED THIS WAIVER WITH ITS COUNSEL.

         IN WITNESS WHEREOF, the undersigned Guarantor has executed this
Guaranty as an instrument under seal under the laws of the Commonwealth of
Massachusetts, as of this 29th day of July, 2003.

Date  July 29, 2003                 By: /s/ John G Conley
                                        -----------------

                                    Title: CFO

                                       3