# Transcriptional control, targeted modification, and excision of HIV in the brain

> **NIH NIH R01** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2020 · $613,101

## Abstract

Project Summary
Transcriptional control, targeted modification, and excision of HIV-1 in the brain
Human Immunodeficiency Virus type 1 (HIV) is a lentivirus that causes a persistent infection, which
ultimately results in the demise of immune regulatory cells. HIV infection is inexorably followed by
diseases attributable to acquired immunodeficiency syndrome (AIDS) (1, 2). Clearance of HIV
infection by the immune system is inefficient and thus allows for integration of proviral DNA into the
genome of host cells, which ultimately results in viral latency (3). Latency in HIV infection has
immense importance because infectious virus can remain protected from immune mediated
clearance and re-emerge after a long absence, often years following initial infection, regardless of
current therapeutic strategies. One location of latent virus is in the brain, an area that is relatively
compartmentalized from the body via the blood brain barrier. HIV infection in the brain results in
NeuroAIDS, a pathological condition that is marked by HIV associated dementia (HAD) (4).
Indubitably, devising a method that would abrogate the viruses' ability to remain in the brain of
infected individuals could prove therapeutically significant and impacting. We propose here to
contrast three distinct, yet complimentary, approaches capable of specifically targeting HIV in the
brain and either epigenetically silencing, directing Cytosine to Thymine (C->T) mutations, or excising
the virus from integrated sites. The three distinct approaches which we will develop here are; (1)
small non-coding RNA directed epigenetic silencing of HIV-1 (5), (2) BREC1 enzymatic cutting of HIV
(6), and (3) a newly developed Zinc Finger targeted silencing and APOBEC1 mediated cytosine to
thymine mutation approach.

## Key facts

- **NIH application ID:** 9870945
- **Project number:** 5R01MH113407-04
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** Kevin V Morris
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $613,101
- **Award type:** 5
- **Project period:** 2017-04-14 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870945

## Citation

> US National Institutes of Health, RePORTER application 9870945, Transcriptional control, targeted modification, and excision of HIV in the brain (5R01MH113407-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9870945. Licensed CC0.

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