Methods and Compositions for CRISPR/Cas9-Mediated Huntingtin Gene Editing

Publication Number: US20250290069A1
Filing Date: April 23, 2025
Publication Date: November 27, 2025
Assignee / Applicant: Sarepta Therapeutics, Inc.
Inventors: Ami M. Kabadi, Xinzhu Wang, et al.

What It Covers

This patent application discloses CRISPR/Cas9 gene editing constructs and associated methods for targeting and modifying the huntingtin gene (HTT) — a key mutation responsible for Huntington’s disease — with the goal of reducing mutant huntingtin protein expression. The technology described includes:

1. CRISPR/Cas9 gene editing systems:

The application covers engineered CRISPR-Cas9 constructs and guide RNAs specifically designed to recognize and cleave target sequences in the huntingtin gene.
These systems rely on delivering Cas9 endonuclease together with one or more guide RNAs that direct the nuclease to precise HTT sequences for targeted genome modification.

2. Methods for editing HTT in patients:

The patent describes methods for administering these CRISPR systems into cells (ex vivo or in vivo) to disrupt, correct, or delete pathogenic segments of the HTT gene.
By doing so, the technology aims to reduce production of the toxic mutant huntingtin protein, which drives neurodegeneration in Huntington’s disease.

3. Therapeutic applications:

It explicitly covers the treatment of Huntington’s disease using the CRISPR systems, making it clinically and commercially relevant to a major unmet genetic disease.
The methods could include delivery strategies (e.g., viral vectors or nanoparticle delivery) tailored to achieve effective editing in the brain and central nervous system.

Why It’s Important

Broad Therapeutic Impact

Huntington’s disease is a devastating, currently untreatable neurodegenerative disorder caused by a single gene mutation. A CRISPR-based therapeutic capable of directly modifying the HTT gene could represent one of the most transformative treatments in neurology, with multi-billion-dollar commercial potential if successfully developed and approved.

Platform Expansion Beyond DMD

While Sarepta’s headline product Elevidys (delandistrogene moxeparvovec-rokl) focuses on Duchenne muscular dystrophy, this patent signals a strategic move into genome editing for other genetic diseases — diversifying its pipeline and reducing reliance on a single franchise.

Competitive IP Position in CRISPR Therapeutics

Owning foundational patents on CRISPRmediated gene editing for Huntington’s disease can provide Sarepta with valuable intellectual property leverage — both for internal development and in out-licensing or partnership negotiations with larger biopharma companies focused on neurological CRISPR therapies.

Alignment with Clinical & Market Trends

CRISPR gene editing is one of the most rapidly advancing modalities in biotech, with first-in-class therapies emerging in clinical trials across multiple diseases. Having early patent priority in this domain strengthens Sarepta’s foothold as gene editing startups and established companies expand their pipelines.

Summary

US20250290069A1 — filed April 23, 2025 and published November 27, 2025 — covers CRISPR/Cas9 gene editing constructs and methods for modifying the huntingtin (HTT) gene to treat Huntington’s disease. This patent is strategically important because it positions Sarepta in the high-value genetic editing therapeutics space beyond its Duchenne muscular dystrophy portfolio, addressing a major unmet need and potentially unlocking a new long-term revenue stream.

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