# CRISPR-Cas9 editing in C9orf72 patient derived iPSC

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $54,000

## Abstract

PARENT PROJECT SUMMARY/ABSTRACT
A heterozygous hexanucleotide (GGGGCC) repeat expansion in a single allele of the C9orf72 gene is the most
frequent genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), two fatal
and irreversible neurodegenerative diseases without effective treatment. Given that the cellular dysfunction
caused by this mutation is multifactorial, targeting the gene itself by CRISPR/Cas9 gene editing is a potentially
curative intervention.
This work proposes novel applications of CRISPR gene editing technology to edit or silence the pathogenic
C9orf72 disease gene in FTD/ALS patient derived iPSC. Three editing strategies will be evaluated for ability to
correct the pathologic C9orf72 repeat expansion, including: A) excising exon 1a to silence transcription of the
repeat expansion, B) excising the repeat expansion itself, C) allele-specific inactivation of the mutant allele
(Aim 1a). In addition, the efficiency of gene editing, off target effects, and ability to correct cellular pathology
will be investigated in C9FTD/ALS patient-derived neurons and microglia (Aim 1b). Finally, new single-
molecule sequencing technology to accurately measure the repeat expansion size will be employed to size the
repeat expansion in various patient iPSC lines and human tissue (Aim 2). This work combines novel
CRISPR/Cas9 editing technologies, cellular disease modeling, molecular and genomic analysis, and
bioinformatics to address these aims.
My goal in seeking a K08 Mentored Clinical Scientist Research Career Development Award is to acquire the
necessary knowledge and scientific training to launch my career as an independent R01 funded academic
investigator. My long-term goal is to make major advances in the therapeutic approaches to neurodegenerative
diseases, including dementias. My doctoral and clinical training provide me with the impetus to address
clinically relevant and high impact hypothesis driven research questions. The exceptional research
environment at the UCSF affiliated Gladstone Institutes combines leaders across many fields with cutting-edge
technology and equipment. I have assembled a team of highly accomplished mentors and advisors to guide
me on my path to becoming an independent investigator. My training plan is designed to advance my technical
skill set in areas that are new to me (CRISPR gene editing, genomic analysis, bioinformatics, and advanced
cellular disease modeling) as well as provide experience in areas critical to successfully running a lab
(scientific communication and lab management). Completing the research and obtaining the skill set I propose
here will prepare me well to obtain an R01 or equivalent funding to launch my career as an independent
investigator.

## Key facts

- **NIH application ID:** 10405372
- **Project number:** 3K08NS112330-02S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Claire Clelland
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2021-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10405372

## Citation

> US National Institutes of Health, RePORTER application 10405372, CRISPR-Cas9 editing in C9orf72 patient derived iPSC (3K08NS112330-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10405372. Licensed CC0.

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