Technology from Kyoto University

RNA Aptamer with Anti-Aggregative Effects against Amyloidosis
We are looking to out-license the technology for its commercialization.

RNA aptamer that binds strongly to the N-terminal region of α-synuclein (αSyn),
thereby exhibiting high inhibitory effects on amyloid aggregation◆Background
Alpha-synuclein (α-Syn) aggregates are associated with neurodegenerative diseases suchas Parkinson's disease, Lewy body dementia, and multiple system atrophy. Although theN-terminal region of αSyn plays an important role in αSyn aggregation, most agents thatdetects αSyn target the C-terminal region, which is susceptible to degradation, making
their practical use challenging. Furthermore, although some antibodies recognize the Nterminal region of αSyn, their large molecular size can hamper drug delivery. Thus, there◆Development Status
Amyloidaggregation

wasinhibited in vitro. The binding
region to αSyn was identified
to be 21-nucleotide sequence.

have been no effective drugs against amyloid diseases.

◆Description◆Applications

RNA aptamers are a type of single-stranded oligonucleotides that bind strongly to specificmolecules. A researcher at Kyoto University identified a novel RNA aptamer that binds toαSyn using 1-95 amino acids located in the N-terminal and the central region of αSyn.

•Therapeutic drugs•

Diagnostic drugs

The identified sequence of the aptamer binding located in the N-terminal region of αSyn
(Fig. 1) and exhibited high inhibitory effects on αSyn aggregation (Fig. 2).
➢ Strong binding to the N-terminal region of αSyn
The C-terminal region of αSyn degraded during the aggregation process, but theN-terminal region remains unprocessed in amyloid fibrils.

◆Offer•Patent License•Option for Patent License➢ Inhibition of amyloid protein aggregation
The novel aptamer is capable of binding to tau in addition to αSyn thus can bepotentially used as a prophylactic or therapeutic agent diverse amyloid diseases.

➢ Aptamer sequence of 21 nucleotides in length
Combined with other methods, delivery to the brain is also possible.
➢ Inexpensive and synthesizable
Imperfect repeat region of KTKEGV
N-terminal
region

KTKEGVmotifs

・Retained in the aggregate・High basic amino acid content

Centralregion

・Prone to defects
・High hydrophobic
amino acid content

C-terminalregion◆Presentations/Papers• 64th Annual Meeting of theJapaneseSocietyofNeurology (June 1, 2023)• 64th Annual Meeting of theJapaneseSocietyfor
Neurochemistry (July 6,2023)• Jikken Igaku (ExperimentalMedicine) Vol.41 No.12

・Prone to defects in theaggregation process・High acidic amino acid content

Drugs for specifically recognizing the N-terminal have not been available to date.
(The N-terminal region plays an important role for aggregation.)Fig. 1 Overview of the Invention
The binding region (1-95) to the aptamer of this invention is highlighted in green.

◆Contact
TLO-KYOTO Co., Ltd.
Mail: event@tlo-kyoto.co.jp
Phone: +81-75-753-9150
Level 5, International Science
Innovation Bldg., Kyoto Univ.,
Yoshidahonmachi, Sakyo-ku,
Kyoto 606-8501, JapanVehicle

RNA Aptamer

Fig. 2 Inhibition of αSyn aggregation by the novel RNA aptamer (HEK293 cells)
An αSyn seeding assay was performed using the FRET method. The novel RNA aptamer inhibitedthe αSyn aggregation, resulting in no FRET (excitation of YFP) signals and decreased aggregation
seeds (puncta) shown in green.