# Establishing a novel gene editing strategy for BBS7 using human retinal organoids

> **NIH NIH K99** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $89,524

## Abstract

PROJECT SUMMARY/ABSTRACT
As the leading cause of inherited retinal degeneration, retinitis pigmentosa (RP) affects about 1.5 million people
worldwide. Bardet-Biedl syndrome (BBS) is the second most common causes of syndromic RP, and is
characterized as an autosomal recessive ciliopathy with severe photoreceptor degeneration occurring by the first
or second decade of life. BBS has been linked to variants in 21 genes, with those in BBS7 accounting for roughly
2% of all BBS cases. The overall goal of this proposal is to overcome two major hurdles in vision research: (1)
the ability to accurately recapitulate disease mechanisms and progression for BBS7 in a translatable model
system, and (2) the ability to permanently correct disease-causing variants and restore photoreceptor cell
function with high efficiency and specificity. In Aim 1, disease mechanisms responsible for the onset of BBS7
will be examined by generating a retinal organoid model system from human induced pluripotent stem cells
harboring disease-causing mutations in the BBS7 gene. In Aims 2 and 3, BBS7 variants will be corrected using
prime editing tools and a lipid nanoparticle (LNP)-based delivery strategy within the human retinal organoid
model to study timing and efficiency of disease rescue. Furthermore, the therapies found to be most effective in
vitro will be tested in nonhuman primates to determine dose, immunogenicity, and efficiency of Cas9 delivery
into photoreceptor cells in vivo. Successful completion of these aim will 1) contribute to our basic understanding
of the pathophysiological mechanisms underlying photoreceptor dysfunction in BBS7, 2) provide the field with a
thorough evaluation of a targeted gene editing strategy to treat BBS7 in the retina, and 3) establish LNPs as an
ideal delivery system to limit cytotoxic and immunologic side effects commonly observed with AAV-based
delivery methods. Taken together, this work will establish a pipeline for testing and optimization of therapies to
treat BBS7 and other inherited retinal diseases, including additional forms of BBS as well as RP.

## Key facts

- **NIH application ID:** 10427680
- **Project number:** 1K99EY033833-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kathleen R Chirco
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $89,524
- **Award type:** 1
- **Project period:** 2022-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427680

## Citation

> US National Institutes of Health, RePORTER application 10427680, Establishing a novel gene editing strategy for BBS7 using human retinal organoids (1K99EY033833-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10427680. Licensed CC0.

---

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