# Therapeutic Development of RNAi-based inhibitors against the Hepatitis Delta Virus

> **NIH NIH R44** · SOMAGENICS, INC. · 2020 · $965,488

## Abstract

Abstract
Hepatitis D virus (HDV) infection is the most severe type of viral hepatitis, often causing
accelerated liver damage that leads to end-stage liver disease. About 15–20 million
individuals are infected by HDV worldwide. The absence of an effective treatment for
acute forms of the disease and the limited efficacy of current treatments for the chronic
infection justify novel strategies towards the development of anti-HDV therapeutics. The
lack of HDV-encoded “druggable” targets that are suitable for conventional therapeutic
modalities such as small molecules and antibodies makes RNA interference an
attractive alternative approach to target this virus. However, the highly structured, GC-
rich circular genome of this smallest of RNA viruses make it a challenging target for
RNA-targeting approaches such as RNAi. In Phase I of this project, we were able to
identify inhibitors of HDV using SomaGenics' sshRNA® (synthetic small shRNAs)
platform. These sshRNAs potently inhibit viral replication at multiple target sites in a cell
culture infection model. The sshRNAs were then chemically modified to improve their
drug-like properties. In Phase 2, we plan to move the program forward into preclinical
studies using a transgenic mouse model that supports HDV infection. We will pursue
dual approaches to delivery of our therapeutic sshRNAs to liver: formulation with lipid
nanoparticles and use of a targeting ligand. Patterns of chemical modification will be
optimized for each candidate delivery method to permit a careful comparison, and the
most promising approach will be selected. Finally, combinations of sshRNAs will be
assessed for ability to provide increased efficacy and forestall the development of
resistance to therapy. By the end of Phase II, we expect to have established a cocktail of
inhibitors ready for IND-enabling safety studies and then commencement of clinical
studies.

## Key facts

- **NIH application ID:** 9905348
- **Project number:** 5R44AI104007-04
- **Recipient organization:** SOMAGENICS, INC.
- **Principal Investigator:** Brian H. Johnston
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $965,488
- **Award type:** 5
- **Project period:** 2014-09-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9905348

## Citation

> US National Institutes of Health, RePORTER application 9905348, Therapeutic Development of RNAi-based inhibitors against the Hepatitis Delta Virus (5R44AI104007-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9905348. Licensed CC0.

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