# Research Core (Deverman)

> **NIH NIH U19** · BROAD INSTITUTE, INC. · 2024 · $2,188,795

## Abstract

ABSTRACT — RESOURCE CORE
Prion disease is a fatal, untreatable neurodegenerative disease caused by the prion protein (PrP). PrP,
encoded by the chromosomal gene PRNP and expressed ubiquitously in all mammals, is not pathogenic in its
native state, but causes disease when it misfolds into a "prion" capable of conformationally corrupting other
PrP molecules. The goal, uniting all arms of this proposal, is to develop a single-dose, permanent PrP-lowering
gene therapy to treat, prevent, or delay prion disease. Our multi-disciplinary team combines the leadership of
committed patient-scientist, prion biologist and lead PI Sonia Vallabh with the cutting-edge expertise pertaining
to base editing from the David Liu Group, epigenome editing from the Jonathan Weissman Lab, and delivery
vector engineering and manufacturing from the Ben Deverman Lab, which will serve as the Vector Core.
Cross-cutting all areas of this proposal is the need for vectors that can achieve dramatically enhanced CNS
gene delivery for this whole brain disease in human patients as well as preclinical models. This need makes
critical the integration of new breakthroughs in delivery vector engineering as well as expertise in vector
biology, production, quality control, and characterization. Through other ongoing, fully funded projects, the
Deverman lab has engineered improved delivery vectors for the CNS and established a platform for
systematically identifying additional vectors with multiple traits relevant to gene therapy. This proposal will
apply the top candidates from these ongoing projects to the development of a PrP-lowering gene therapy. The
Vector Engineering Resource Core led by Dr. Deverman will undertake process development, production,
formulation, and characterization of delivery vectors in support of the in vivo studies for all three projects in this
proposal; assist with tissue handling and biodistribution analysis; develop a scalable production and analytical
pipeline, and provide technology transfer and oversight for at-scale manufacturing. In the context of this overall
proposal, the Resource Core will underpin the core goal of transforming prion disease therapy with a single-
dose therapy, and also provide a foundational proof-of-concept for the application of engineered delivery
vectors toward systemically-administered CNS gene therapy in adult human patients.

## Key facts

- **NIH application ID:** 10843168
- **Project number:** 5U19NS132315-02
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Benjamin E Deverman
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,188,795
- **Award type:** 5
- **Project period:** 2023-05-17 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843168

## Citation

> US National Institutes of Health, RePORTER application 10843168, Research Core (Deverman) (5U19NS132315-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10843168. Licensed CC0.

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