# Project 1: Therapeutic Gene Editing for Spinal Muscular Atrophy (Trailblazer)

> **NIH NIH U19** · JACKSON LABORATORY · 2024 · $548,986

## Abstract

PROJECT SUMMARY PROJECT 1 (SMA)
Spinal Muscular Atrophy (SMA) is a progressive motor neuron disease (MND) and the leading genetic cause of
infant mortality across all ethnic groups. SMA is caused by the homozygous loss of the essential survival motor
neuron 1 (SMN1) gene and while one or more copies of the highly similar SMN2 gene partially compensates for
the loss of SMN1 in SMA patients, SMN1, in contrast to SMN2, contains a C·G-to-T·A change at position 6 of
exon 7 (C6T). This change leads to skipping of exon 7 during mRNA splicing and the resulting truncated SMNΔ7
protein is rapidly degraded in cells. This rapid degradation results in SMN protein insufficiency, loss of motor
neurons, paralysis, and death. Patients with the most common form of SMA, type I, have a ~10-fold reduction in
SMN protein levels and live to a median age of 6 months if untreated.
In this trailblazer project, we aim to (1) Optimize base editing treatment protocols in Δ7 SMA mice; (2) Assess
biodistribution, off-targets, and toxicity profiles in SMA mice; and (3) Conduct large-scale efficacy studies. We
will work closely with the Gene Editing core to generate rigorous analyses of gene editing outcomes for the IND
submission of our trailblazer project, and we will coordinate closely with the Preclinical Mouse Model Core to
analyze samples from large-scale efficacy studies. The successful outcomes of this trailblazer project will also
inform the strategies used to develop genome editing-based therapeutic leads in all Follower Projects.

## Key facts

- **NIH application ID:** 10842410
- **Project number:** 5U19NS132304-02
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Mandana Arbab
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $548,986
- **Award type:** 5
- **Project period:** 2023-05-16 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842410

## Citation

> US National Institutes of Health, RePORTER application 10842410, Project 1: Therapeutic Gene Editing for Spinal Muscular Atrophy (Trailblazer) (5U19NS132304-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842410. Licensed CC0.

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