TARGETING OF OSTEOSARCOMA CELLS THROUGH ARTIFICIAL EVOLUTION OF THE FELINE LEUKEMIA VIRUS ENVELOPE PROTEIN: SELECTION FOR A DISULPHIDE BOND WITHIN THE VARIABLE REGION A
Leonardo Valdivieso-Torres Sr.1, Anindita Sarangi1, Jill Whidby2, Zheng Hayian3, Joseph Marcotrigiano2, Monica Roth1.
1Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, 2Center for Advanced Biotechnology and Medicine-Rutgers University, Piscataway, NJ, 3Rutgers University, Piscataway, NJ.
Retroviral vectors are exceptional vehicles for gene delivery. As a result, they hold great therapeutic potential for treating a variety of diseases including cancer. However, in order to realize this potential, the engineered viral vectors must be highly specific for the appropriate tissue or cancer targeted. The specificity of retroviral vectors is conferred by the envelope (Env) protein present on the surface of virus particles and is responsible for binding a host-cell receptor, thereby initiating virus entry. We successfully generated a library of peptides by randomizing 11 residues of the receptor-binding domain of the feline leukemia virus Env protein and screening for functional Envs specific to osteosarcoma cells. We are reporting 9 new isolates, mutagenesis, and mass spectrometry studies of the best Envs. This study validates our technique to obtain novel re-targeted Env proteins and shear lights into understanding the rules for optimal library screenings that will assist in the design of third-generation Env libraries. The overall goal of our research is to identify novel retroviral Env host cell-receptor pairs to facilitate targeted gene delivery.