CD4-Nanoparticle Conjugates for the Treatment of HIV/AIDS
Background:
The Laboratory of Cell Biology of
the National Cancer Institute is seeking statements of capability
or interest from parties interested in collaborative research to
further develop, evaluate, or commercialize polyvalent antiviral
dendritic conjugates for the treatment of HIV.
Human immunodeficiency virus type 1 (HIV-1) infection of target
cells is initiated by binding of the viral envelope glycoprotein
gp120 to the cell surface receptor CD4. D1D2-IgP is a dodecameric
CD4-immunoglobulin fusion protein with sub-nanomolar HIV
neutralizing potency against patient isolates, capable of viral
rupture. However, due to its high molecular weight and
polydispersity, this fusion protein cannot be used as an HIV
drug.
Technology:
This technology describes the
structure-based design and synthesis of monodisperse, homogeneous,
CD4-nanoparticle conjugates that mimic the D1D2-IgP fusion protein.
These conjugates comprise a soluble, two-domain human CD4
covalently linked to a flexible dendrimer-PEG scaffold. The
construct is designed to mimic the structure of D1D2-IgP, and, at
173 kDa, is similar in size to successful antibody therapeutics
currently on the market.
Because it retains the key elements of potency and the polyvalent
human CD4 moieties of D1D2-IgP, this conjugate is expected to
afford the same antiviral properties in a monodisperse,
homogeneous, and low-molecular-weight species.
Further R&D
Needed:
- Commercial optimization of existing strategies for expressing
and purifying a protein-engineered CD4 mutant, and of
protein-nanoparticle conjugate assembly reaction
- Infectivity neutralization assays against a wide range of
clinical isolate HIV strains
- Pharmacologic characterization, e.g., in vivo half-life
- Testing of pre- and/or post-exposure prophylaxis
(person-to-person and mother-to-child)
- Testing as a topical microbicide
R&D Status: Discovery.
Proof-of-concept underway.
IP Status: U.S.
Provisional Application No. 60/932,464 filed 31 May 2007
Value
Proposition--Solution:
A CD4 therapy that
overcomes previous failures by addressing conformational masking:
- Mimics the most powerful HIV-neutralizing protein
- Effective against all CD4-dependent strains
- Monodisperse, homogeneous
Contact
Information:
John D. Hewes, Ph.D., NCI
Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov
Reference: #619 KH
Posted 02/09/2008