# Gene edited B cells to co-express CNS-targeted antibodies

> **NIH NIH R21** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $206,250

## Abstract

ABSTRACT
 The CNS is a viral reservoir in HIV-infected individuals, 50% of whom will eventually develop HIV-
associated neurodegeneration (HAND), despite antiretroviral drugs. Antibodies can also be powerful antivirals,
promoting virus neutralization and the removal of HIV-infected cells through mechanisms such as ADCC and
ADCP. Of special interest are broadly neutralizing antibodies (bnAbs), which can recognize the Env proteins
from diverse viral strains and are therefore somewhat resistant to viral escape. As such, bnAbs are considered
a promising approach for treating or preventing HIV infection, although the lack of induction of bnAbs by
vaccination means that they are currently only used as injected proteins, or expressed from gene therapy vectors
in non-immune tissues. An additional concern for CNS infections is that antibodies are present at lower rates in
the CNS than the blood, although this can be enhanced by the addition of brain penetrating modules to the
antibody.
 We have developed a gene editing strategy that allows us to reprogram human B cells to express specific
antibodies. Our strategy takes advantage of the ability of B cells to respond to the presence of their cognate
antigen, resulting in long-term secretion of the engineered antibody. We will now adapt this strategy to allow the
co-expression of both bnAbs and modified brain-penetrating antibodies (BP-Ab) from the same edited cells.
Using a range of assays, we will evaluate whether BP-Abs expressed from edited B cells retain full anti-HIV
activities and show enhanced delivery to the CNS. In this way we will have developed the necessary proof of
concept that a B cell therapy could be developed to provide long-term, HIV-responsive expression of brain-
penetrating bnAbs.

## Key facts

- **NIH application ID:** 10475527
- **Project number:** 1R21MH130178-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Paula M Cannon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $206,250
- **Award type:** 1
- **Project period:** 2022-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475527

## Citation

> US National Institutes of Health, RePORTER application 10475527, Gene edited B cells to co-express CNS-targeted antibodies (1R21MH130178-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10475527. Licensed CC0.

---

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