# Evaluation of Self-delivering FANA Antisense Oligonucleotide Lead Compounds for HIV Therapy

> **NIH NIH R43** · AUM LIFETECH, INC. · 2021 · $300,000

## Abstract

Project Summary/Abstract:
Human immunodeficiency virus 1 (HIV-1) is the primary cause of acquired immune deficiency syndrome (AIDS)
that affects over a million people in the United States alone. Advances in treatment have significantly prolonged
the lives of those infected with HIV-1, with combinatorial antiretroviral therapy (cART) being the current standard
in therapeutic care. However, cART alone cannot achieve complete eradication of the virus. Besides, drawbacks
such as drug resistance development and severe side effects (e.g. premature aging, cancer, and cardiovascular
disease) remain critical issues in cART therapy. Therefore, there is a need for a treatment, with efficient delivery
and a favorable safety profile, that can reduce the HIV-1 viral load to undetectable levels. A promising approach
is to utilize RNA silencing to treat HIV-1 infection by targeting the dimerization initiation site (DIS), a replication
signal in the 5’ untranslated region (5’-UTR). Dimerization is initiated when the 5'-UTR undergoes a
conformational change, allowing the DIS loops of two RNA genomes to base pair. This forms a kissing-loop (KL)
dimer, which then leads to the subsequent packaging of the viral RNA. It is known that mutation or inhibition of
the DIS severely restricts viral infectivity. Here we propose to test if 2’-deoxy-2’-fluoro-D-arabinonucleic acid
antisense oligonucleotides (FANA ASOs), targeting DIS, will prevent viral replication. FANA ASOs will be
designed to cleave (RNase H-dependent) or block viral RNA, thus inhibiting viral replication post-exposure. In a
preliminary study using HIV-1 infected human peripheral blood mononuclear cells (PBMCs), DIS-targeting
FANAs inhibited HIV-1 replication for as long as two weeks, after single doses of 400 nM and 3 µM doses (IC50
= 200 nM). FANA ASOs were also tested as prophylactics in vitro, at significantly lower concentrations, to prevent
viral infection and amplification for up to 2 weeks. FANA ASOs were also designed to bind to DIS RNA without
cleaving it, which would prevent the formation of the kissing loop structure that is necessary for replication. AUM-
DIS-G9 emerged as the lead compound from our RNase H-dependent in vitro studies, while AUM-DIS-G0 will
be the lead compound for our RNase H-independent trials. In this study, we will adopt a systematic approach to
design and assess these two FANA lead ASOs targeting DIS. Our first aim is to evaluate the reduction in viral
replication after treating with our two lead compounds, from our preliminary data, in a humanized NSG mouse
model susceptible to HIV-1 infection. The second aim is to assess the potential of FANA ASOs as cART
replacement in vivo, considering their prophylactic success in vitro, in a latently infected humanized mouse
model. The third Aim is to perform standard pharmacokinetic and ADME studies on the lead compound from
Aims 1 and 2 in vivo assessments. The goal of the proposed study is the development of a next generation
antisen...

## Key facts

- **NIH application ID:** 10232090
- **Project number:** 5R43AI152774-02
- **Recipient organization:** AUM LIFETECH, INC.
- **Principal Investigator:** Veenu Aishwarya
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $300,000
- **Award type:** 5
- **Project period:** 2020-08-07 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10232090

## Citation

> US National Institutes of Health, RePORTER application 10232090, Evaluation of Self-delivering FANA Antisense Oligonucleotide Lead Compounds for HIV Therapy (5R43AI152774-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10232090. Licensed CC0.

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