EPSTEIN-BARR-VIRUS VECTORS FOR GENE DELIVERY TO B-LYMPHOCYTES

Basic research in Epstein-Barr virus (EBV) molecular genetics has prov ided means to maintain episomes in human cells, to efficiently deliver episomes with up to 150 kbp of heterologous DNA to human B lymphocyte s, and to immortalize human B lymphocytes with EBV recombinants that c an maintain up to 120 kbp of heterologous DNA. Episome maintenance req uires an EBV nuclear protein, EBNA1, whereas immortalization of cells with EBV recombinants requires EBNA1, EBNA2, EBNA3A, EBNA3C, EBNALP, a nd LMP1. EBV-derived vectors are useful for experimental genetic recon stitution in B lymphocytes, a cell type frequently used in establishin g repositories of human genetic deficiencies. The ability of EBV-infec ted cells to establish a balanced state of persistence in normal human s raises the possibility that cells infected with EBV recombinants cou ld be useful for genetic reconstitution, in vivo.