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

> **NIH NIH R00** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $248,998

## 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:** 10928808
- **Project number:** 5R00EY033833-04
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Kathleen R Chirco
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $248,998
- **Award type:** 5
- **Project period:** 2022-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10928808

## Citation

> US National Institutes of Health, RePORTER application 10928808, Establishing a novel gene editing strategy for BBS7 using human retinal organoids (5R00EY033833-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10928808. Licensed CC0.

---

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