# Research Project II: AAV-CRISPR to Treat Amyotrophic Lateral Sclerosis

> **NIH NIH U19** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $567,041

## Abstract

PROJECT SUMMARY/ABSTRACT
A heterozygous hexanucleotide (GGGGCC) repeat expansion in a single allele of the C9orf72 gene is the most
frequent known genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two
fatal and irreversible neurodegenerative diseases. Given that there are no effective treatments for FTD (an
Alzheimer’s-related dementia) and ALS, novel therapeutic strategies are urgently needed. Targeting the
C9orf72 gene itself by CRISPR/Cas9 gene editing may provide a curative intervention.
With the completion of the proposed IND-enabling studies, we will have developed a platform for allele-specific
gene therapy of the human mutant C9orf72 gene combining novel allele-specific editing with a novel AAV-LC.V1
convection-enhanced delivery platform. We will have addressed a number of open questions in the field,
including whether editing efficiencies in post-mitotic neurons differ from mitotic cells, how to deliver
CRISPR/Cas9 with multiple gRNAs to motor neurons in the cortex and spinal cord of mouse, whether it is
possible to reverse clinical phenotypes in pre-symptomatic vs. symptomatic mice, and whether CRISPR self-
deactivation decreases unwanted off-target editing and immune response in mice. The results of our experiments
will lead to rational design of IND dose finding studies in non-human primates and toxicology studies in rats,
inform clinical trial design, and accelerate gene editing for neurodegenerative disease toward the clinic.

## Key facts

- **NIH application ID:** 10840865
- **Project number:** 5U19NS132303-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Claire Clelland
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $567,041
- **Award type:** 5
- **Project period:** 2023-05-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840865

## Citation

> US National Institutes of Health, RePORTER application 10840865, Research Project II: AAV-CRISPR to Treat Amyotrophic Lateral Sclerosis (5U19NS132303-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10840865. Licensed CC0.

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