# Open-Access AAV Toolbox for Basal Ganglia Cell Types and Circuits

> **NIH NIH UF1** · ALLEN INSTITUTE · 2021 · $7,282,237

## Abstract

Project Summary
We propose to leverage new and existing transcriptomic and epigenetic datasets from mouse, marmoset,
macaque and human brain to develop refined approaches for brain cell type enhancer selection for creating cell-
type specific enhancer adeno-associated viruses (AAVs), and to make inroads toward prediction of brain-wide
expression specificity. We will focus on basal ganglia (BG) cell types for several reasons: 1) BG encompass
several brain areas with different embryonic origins and cellular complexity, 2) BG are integral for motor output
and reward pathways and have thus been highly conserved through evolution, and we predict many BG
enhancers can be found that are conserved across species, 3) BG dysfunction is a shared feature of many brain
disorders, and AAV vectors that target BG cell types with high specificity will be useful for basic and translational
research, and 4) sufficient epigenetic data are now available that cover BG structures in mouse, marmoset,
macaque and human, and our preliminary analysis supports the feasibility of utilizing these data sources for
discovery of striatum-specific enhancers with a high success rate.
To create a suite of viral tools for BG cell types, we propose to create an end-to-end screening and validation
pipeline for discovery of brain cell type enhancer AAVs at the Allen Institute. Multiple epignomic and
transcriptomic datasets will be consolidated and interrogated to reveal candidate enhancers that are selectively
accessible in the BG cell populations. Enhancer AAVs will be constructed and screened for desirable expression
either singly or in multiplexed approaches. A sizeable subset of enhancer AAVs will be subjected to molecular
characterization by single cell transcriptomics and/or multiplexed FISH to reveal specificity and completeness of
labeling for each virus, as well as brain-wide expression mapping in mouse with serial two-photon tomography.
We will deliver a collection of novel viral tools for BG cell types that have been validated for high specificity and
completeness of labeling in vivo in both mouse and macaque. Furthermore, we will create an open-access online
atlas that will display detailed AAV characterization data. Lastly, we will develop a partnership with Addgene and
leverage their self-sustaining and scalable model for plasmid DNA and virus distribution to the scientific
community. We will track plasmid and vector requests from our collection to measure the impact of our vectors
for the wider research community.
If successful, this pilot award will establish a roadmap for integrated analysis of diverse epigenetic datasets for
cell type enhancer discovery, scalable enhancer AAV screening methods in the mouse and non-human primate
brain, and widespread distribution of knowledge and tools to the research community. Although we focus our
efforts on BG cells types and circuits in this pilot U01 project, our goal is to build a scalable pipeline that is
generalizable to cell ...

## Key facts

- **NIH application ID:** 10350021
- **Project number:** 1UF1MH128339-01
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Trygve Bakken
- **Activity code:** UF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $7,282,237
- **Award type:** 1
- **Project period:** 2021-09-16 → 2024-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350021

## Citation

> US National Institutes of Health, RePORTER application 10350021, Open-Access AAV Toolbox for Basal Ganglia Cell Types and Circuits (1UF1MH128339-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10350021. Licensed CC0.

---

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