Griffithsin, a Novel anti-HIV Protein with Potential Microbicidal, Therapeutic and/or Purification Utilities
Background:
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.
Technology:
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
- Potential therapeutic agent for systemic use similar to
Fuzeon
- Potential use in purifying biological fluids from HIV
virions
Current State of
Development:
- The crystal structure of GRFT has recently been published.
- On-going in vitro evaluation against additional viruses.
- In vivo mucosal irritancy studies competed.
- Pre-clinical 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.
IP Status:
U.S. Patent Application filed on June 1, 2004
Contact
Information:
John D. Hewes, Ph.D., NCI
Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #27 MC
Updated 11/02/2007
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