# Mapping the assembly pathways for viral capsids by direct single-particle measurements

> **NIH NIH K99** · HARVARD UNIVERSITY · 2020 · $99,999

## Abstract

Project Summary
 The capsids of many RNA viruses spontaneously assemble around the viral RNA in the cytoplasm of an
infected host cell. Mapping out the assembly pathway—that is, the set of molecular rearrangements that produce
the final infectious structure—is the first step toward developing antiviral drugs that block the process and halt
the spread of pathogenic viruses. Available experimental techniques, which measure what happens in a bulk
solution of capsids and not in individual capsids, obscure the essential kinetics. As a result, we lack answers to
basic questions about how capsids form, such as whether the rate limiting step is nucleation, or growth, or the
rearrangement of coat proteins following an initial disordered attachment to the RNA.
 New tools from nanoscience can tackle these challenges. This proposal describes a plan to measure and
understand capsid assembly in vitro at the single-capsid scale: a powerful nanoscale imaging technique called
interferometric scattering (iSCAT) microscopy is applied to monitor the growth of individual viral capsids on
individual strands of RNA. The data from these measurements can be used to build new models of the assembly
pathway that describe the process in unprecedented detail. Special focus is paid to the role of the viral RNA in
directing these pathways. New DNA-based techniques are developed to unravel the complex folding patterns of
viral RNA and to selectively probe the specific RNA-protein interactions that have been proposed to play a role
in capsid assembly. The combined approach of fast nanoscale imaging and DNA-based methods for
manipulating specific molecular interactions may reveal unexpected routes for blocking capsid assembly and
combating viral disease.

## Key facts

- **NIH application ID:** 9852605
- **Project number:** 5K99GM127751-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Rees F Garmann
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $99,999
- **Award type:** 5
- **Project period:** 2019-02-01 → 2021-01-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852605

## Citation

> US National Institutes of Health, RePORTER application 9852605, Mapping the assembly pathways for viral capsids by direct single-particle measurements (5K99GM127751-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9852605. Licensed CC0.

---

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