# Chemically modified siRNA drugs for ocular disease

> **NIH NIH R43** · ADVANCED RNA TECHNOLOGIES, LLC · 2020 · $294,022

## Abstract

ABSTRACT
Current treatments of some ocular diseases require frequent injection of therapeutics into the eye, sometimes
as often as every month. This puts a significant burden on both patients and healthcare systems. In clinical
practice injections are often done less frequently than is required, which limits efficacy and leads to disease
progression and loss of vision. There is therefore a need for therapeutics that can provide much longer
duration of action from each injection. Recent developments in RNAi chemistry and delivery have produced a
class of therapeutics that can provide potent silencing of target genes in tissues of up to 12 months, from a
single injection, which is an almost vaccine like effect. Several therapeutics based on this technology are in
late stage of clinical development and have proven to be effective and very safe in large phase II and III trials.
This project aims to develop a therapeutic based on fully chemically modified siRNA conjugates with much
longer duration of action in the eye than currently used therapeutics, at least up to six months from a single
injection.
We have previously screened a set of 250 siRNA compounds and have identified several lead candidates
targeting the VEGF gene. In the proposed project, we aim to test our lead siRNA conjugates in animal models
to validate the long term efficacy and safety, and to optimize the compounds to further improve potency,
stability and safety.
We aim to achieve this goal by:
 1. Test variants of the compounds in tissue culture to better understand structure-activity relationships.
 2. Optimizing the compound structure for potency and stability, as well as safety.
 3. Testing several conjugated compounds in animals to determine medium term efficacy and duration of
effect.
 4. Determining the duration of effect of the therapeutic effect in animal model.
The expected outcome of this project is an optimized siRNA therapeutic that is ready to enter IND enabling
studies. The technology and knowledge developed during the project can also serve as a platform for the
development of additional therapeutics for a range ocular diseases.

## Key facts

- **NIH application ID:** 10081644
- **Project number:** 1R43EY031618-01A1
- **Recipient organization:** ADVANCED RNA TECHNOLOGIES, LLC
- **Principal Investigator:** Alexey Wolfson
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $294,022
- **Award type:** 1
- **Project period:** 2020-09-30 → 2022-03-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10081644

## Citation

> US National Institutes of Health, RePORTER application 10081644, Chemically modified siRNA drugs for ocular disease (1R43EY031618-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10081644. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*