# In vivo CRISPR engineering of B cells to produce anti-HIV broadly neutralizing antibodies using novel nanoparticles

> **NIH NIH R01** · FRED HUTCHINSON CANCER CENTER · 2022 · $877,927

## Abstract

PROJECT SUMMARY / ABSTRACT
The quest for an HIV cure remains incomplete, nearly half a century since the onset of the epidemic.
Antiretroviral drug cocktails can suppress HIV infection, but suffer in their success owing to side effects
and limitations in access and compliance. Injection of broadly neutralizing antibodies (bNAbs) to
prevent HIV rebound has had some success, but requires regular re-injection of multiple antibodies to
maintain suppression and viral escape. Thus, cost and continued access remain limitations. Genetic
engineering of patient cells has been proposed to overcome all of these shortfalls, and could constitute
a one-time treatment with lifelong therapeutic value if successful. In this proposal, we leverage a novel
approach developed by Dr. Justin Taylor’s laboratory to genetically engineer B cells to express bNAbs
for the treatment of human immunodeficiency virus (HIV). This strategy has already been used to
engineer B cells to produce antibodies protective against influenza virus, respiratory syncytial virus,
Epstein-barr virus and HIV [Moffett et al., Science Immunology, 2019]. While this approach can ensure
protective antibody production, the genetic engineering process required 10 days of complicated ex
vivo manufacturing and is not broadly distributable. To overcome these barriers, we will co-opt a novel,
synthetic nanoparticle that was developed in Dr. Jennifer Adair’s laboratory to deliver genetic
engineering in a single, passive step [Shahbazi et al., Nature Materials, 2019]. We show that this
nanoparticle can be assembled in less than a day to genetically engineer unstimulated, primary human
blood cells and can be modified to specifically interact with target blood cell types in vivo. Here we will
develop this scalable nanoformulation as a vaccine-like in vivo delivery system to direct humoral
immunity with multiple bNAbs in a clinically-relevant nonhuman primate model of HIV infection. We will
use these nanoparticles to directly genetically engineer native primary B cell subtypes, and
hematopoietic stem and progenitor cells, which can provide lifelong replenishment of antibody-
producing B cells. This research will not only develop a unique tool set against HIV but will provide
transformative advances in equitable distribution of gene editing therapies.

## Key facts

- **NIH application ID:** 10374397
- **Project number:** 1R01AI167009-01
- **Recipient organization:** FRED HUTCHINSON CANCER CENTER
- **Principal Investigator:** Jennifer Eileen Adair
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $877,927
- **Award type:** 1
- **Project period:** 2022-06-08 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10374397

## Citation

> US National Institutes of Health, RePORTER application 10374397, In vivo CRISPR engineering of B cells to produce anti-HIV broadly neutralizing antibodies using novel nanoparticles (1R01AI167009-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10374397. Licensed CC0.

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