A -- Development of Griffithsin, 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. 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 Escherichia coli. Potential Areas if Application: Potential anti-HIV microbicide as a female-controlled virucidal gel, cream or suppository. Also potential therapeutic agent for systemic use similar to Fuzeon®. Griffithsin also has potential use in purifying biological fluids from HIV virions. Main Advantages of the Technology: Uniquely potent activity against HIV. No toxicity displayed in host cells at highest tested concentrations. Has been produced recombinantly in E. coli. Current State of Development: On-going X-ray crystallographic studies and in vitro evaluation against additional viruses. Continuing efforts on enhanced recombinant production yields. Further R&D Required: In vivo efficacy, immunogenicity, toxicity, pharmacokinetic, ADME and large-scale production studies. Patent Status and Pertinent References: a) U.S. Patent Application filed on June 1, 2004. Contact Information: Bjarne Gabrielsen, Ph.D., Technology Transfer Branch, NCI-Frederick, Fairview Center, Suite 500, 1003 - W. 7th Street, Frederick, MD 21701-8512. Phone: (301) 846-5465; email: [email protected]. Submitted: 9/1/2004