# Gene Silencing and Gene Editing in Phototransduction

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $390,438

## Abstract

Project Summary
Gene-augmentation therapy cannot address autosomal-dominant (ad) disorders, in which a
defective protein is expressed. To treat these mutations, such as the dominant form of rhodopsin
(RHO)-related retinitis pigmentosa RP (adRP), the only cure is to silence (RNAi) or edit the mutant
allele. Precise CRISPR therapeutic editing is predicted to be the best means of treating several
dominant disorders, but molecular methods harnessing CRISPR have been slow to develop
because homology-directed repair (HDR) occurs only during the S and G2 phases of the cell
cycle. To overcome these limitations, we have established a versatile editing technology that uses
2 guide RNAs (gRNAs) to target all 150 dominant RHO mutations at any phase of the cell cycle.
To conduct preclinical evaluation of this species-specific technology, we have replaced the naïve
mouse chromosomal Rho with human RHO mutant sequences (humanized RHO). If successful,
the viral vectors used in our therapeutic editing strategy could be directly reused in human trials
for adRP without further modification, thus avoiding FDA hurdles and accelerating translation of
this research to a clinical setting. Our preclinical adRP model could also be useful for testing of
future gene- and drug-based therapies. The proposed research is innovative, as it introduces
new methods and model systems as the initial steps of a precision medicine approach toward
developing adRP treatment. These methods are also potentially adaptable to therapies based on
targeting DNA sequences of genes linked to other dominant disorders.

## Key facts

- **NIH application ID:** 10246786
- **Project number:** 5R01EY024698-07
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Stephen H Tsang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $390,438
- **Award type:** 5
- **Project period:** 2015-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246786

## Citation

> US National Institutes of Health, RePORTER application 10246786, Gene Silencing and Gene Editing in Phototransduction (5R01EY024698-07). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10246786. Licensed CC0.

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