# RNA Scaffolds for Cell Specific Multiplexed Neural Observation

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2020 · $668,458

## Abstract

Genetically encoded molecular tools are having impact throughout neuroscience. However, each genetically
encoded molecular tool is a feat of protein engineering, requiring extensive effort to design and optimize. One
appealing thought is that it might be possible to create a small number of modular protein building blocks,
which then could be organized in patterns, and achieve user-programmable functions, by being scaffolded
together on strands of RNA. We recently derived from the Pumilio homology domain (PumHD) protein, 4
building blocks, each of which prefers one of the 4 bases of RNA, so that for any RNA of interest in a cell, a
chain made out of the 4 building blocks in a defined sequence can be created to bind to that RNA (bringing
along any protein payloads that are fused to that chain). We propose to adapt this Pumilio based (or “Pum”
for short) strategy to create RNA-scaffolded molecular tools that address two major classes of problem in
neuroscience – the targeting of gene expression to specific cell types in the mammalian brain, with high
specificity, without requiring transgenic animals (Aim 1), and the ability to image multiple independent
fluorescent reporters of physiological activity within individual neurons without crosstalk (Aim 2). We will
assess, and optimize, these scaffolded molecular tools in mice (Aims 1, 2) and a non-genetic model organism
(macaques), aiming to open up new frontiers of neuroscience experimentation (Aim 3). Our grant is a fast-
paced, 4-year grant, which brings together experts in neurotechnology development (Boyden), primate
systems neuroscience (Desimone), and nucleic acid technology (Adamala). We will share all tools freely with
the neuroscience community, in order to broadly accelerate neuroscience progress.

## Key facts

- **NIH application ID:** 9981014
- **Project number:** 5R01MH114031-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Edward S. Boyden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $668,458
- **Award type:** 5
- **Project period:** 2017-08-25 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981014

## Citation

> US National Institutes of Health, RePORTER application 9981014, RNA Scaffolds for Cell Specific Multiplexed Neural Observation (5R01MH114031-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9981014. Licensed CC0.

---

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