NIH Develops a Novel Anti-HIV Protein With Potential Microbicidal, Therapeutic and/or Purification Utilities
The National Cancer Institute (NCI) Molecular Targets Development Program (MTDP) seeks a Cooperative Research and Development Agreement (CRADA) collaborator to develop griffithsin (GRFT), a novel, potent anti-HIV protein isolated from an aqueous extract of the red algae Griffithsia. The main advantages of the technology are its uniquely potent activity against HIV with no toxicity displayed in host cells at highest tested concentrations. It has been produced recombinantly in E. coli.
Sequence analysis reveals that it shares no significant homology with previously described proteins or to the transcription products of known nucleotide sequences. GRFT displayed potent antiviral activity against laboratory strains and primary isolates of HIV-1 with EC50 values ranging from 0.043 to 0.63 nM. In addition, GRFT aborted cell-to-cell fusion at similar concentrations. High concentrations (e.g., 783 nM) of GRFT were not found to be lethal to representative host cell types. GRFT blocks CD4-dependent gp120 binding and binds to viral coat glycoproteins, but not to sCD4 or other tested proteins. GRFT has been recombinantly produced by expression of a corresponding DNA sequence in E. coli.
- Potential anti-HIV microbicide as a female-controlled virucidal gel, cream or suppository
- Potential therapeutic agent for systemic use similar to Fuzeon
- Potential use in purifying biological fluids from HIV virions
- The crystal structure of GRFT has recently been published
- Ongoing in vitro evaluation against additional viruses
- In vivo mucosal irritancy studies competed
- Preclinical evaluation as a potential topical microbicide against HIV ongoing
Further R&D Required:
In vivo efficacy, immunogenicity, toxicity, pharmacokinetic, ADME and large-scale production studies
U.S. Patent application filed on June 1, 2004
For more information, contact John D. Hewes, Ph.D., NCI Technology Transfer Center, 301-435-3121, or Hewesj@mail.nih.gov.