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

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R44AI104007-02A1
Agency Tracking Number: R44AI104007
Amount: $2,885,901.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA17-302
Solicitation Year: 2017
Award Year: 2018
Award Start Date (Proposal Award Date): 2018-04-20
Award End Date (Contract End Date): 2021-03-31
Small Business Information
Santa Cruz, CA 95060-5790
United States
DUNS: 013494781
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (831) 426-7700
Business Contact
Phone: (831) 426-7700
Research Institution

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 SomaGenicsandapos; 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.Health relatedness narrative
About 15 million people who are chronically infected with hepatitis B virus are also
infected the hepatitis delta virus (HDV). There is no curative treatment for HDV. The
only treatment option (alpha interferon) is effective in less than 50% of patients and
withdrawal of the drug leads to relapse. HDV infection can rapidly progress to end-stage
liver disease, for which a liver transplant is the only treatment option. Success in our
novel approach to combatting HDV infection would save countless lives and produce
large savings in the healthcare costs.

* Information listed above is at the time of submission. *

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