eCD4-Ig

eCD4-Ig is an engineered, antibody-like biologic entry inhibitor designed for the treatment and prevention of HIV infection. It is a fusion protein that combines the first two domains of the CD4 receptor (the natural receptor for HIV) with a tyrosine-sulfated peptide that mimics the HIV coreceptors CCR5 and CXCR4, all fused to the Fc region of an IgG1 antibody. This dual-targeting approach allows eCD4-Ig to bind simultaneously to the CD4-binding site and the coreceptor-binding site of the HIV-1 envelope glycoprotein gp120, effectively blocking viral entry. Unlike many broadly neutralizing antibodies (bNAbs), eCD4-Ig has demonstrated the ability to neutralize 100% of tested HIV-1, HIV-2, and simian immunodeficiency virus (SIV) isolates. It is primarily intended for delivery via adeno-associated virus (AAV) gene therapy vectors to provide long-acting protection. The molecule was developed at The Scripps Research Institute and has been supported by SBIR grant funding for manufacturing scale-up toward clinical trials.