# A Novel Hybrid Viral Vector for Therapeutic CRISPR Insertion of Multiple Transgenes

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
Existing delivery systems for CRISPR-Cas gene editing machinery have very little capacity for making multigenic
insertions. As such, the scope of existing gene therapies has been limited primarily to monogenic diseases. Yet
multigenic insertions could facilitate treatment of a much broader range of conditions. To address this challenge,
I am developing a chimeric AdAAV gene editing delivery system by physically linking multiple adeno-associated
viruses (AAVs) to the surface of adenovirus (Ad). I am using the SpyTag-SpyCatcher technology for site-specific
covalent conjugation. In my design, the Ad will encode the Cas9 protein and the gRNAs while the AAVs will
provide a single-stranded DNA template. To enable multigenic genetic insertions, I will conjugate a mixture of
AAVs (with distinct genetic cargos) onto the Ads. Each AAV cargo sequence will undergo programmable
insertion into a unique genomic target site via the Cas9 and gRNAs encoded in the Ad. I anticipate that the strong
and targetable transduction of the Ad will efficiently drive the uptake of AdAAV particles into cells. I also anticipate
that greater in vivo gene editing efficiencies may occur using this design because of the known benefits of single-
stranded DNA templates for homology-directed repair (HDR). My fully novel AdAAV vector will act as an
efficacious and versatile platform for multigenic gene therapy. AdAAVs will be particularly suited for treating
aging and aging-related conditions, especially Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10896740
- **Project number:** 1F31AG084489-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Logan Thrasher Collins
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896740

## Citation

> US National Institutes of Health, RePORTER application 10896740, A Novel Hybrid Viral Vector for Therapeutic CRISPR Insertion of Multiple Transgenes (1F31AG084489-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896740. Licensed CC0.

---

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