USE OF PSEUDOTYPED LENTIVIRAL PARTICLES FOR IN VITRO TARGETED TRANSDUCTION OF UNDIFFERENTIATED PLURIPOTENT HUMAN EMBRYONIC STEM CELLS AND INDUCED PLURIPOTENT STEM CELLS

摘要

The inventors developed novel pseudotyped lentiviral vector particles comprising a morbillivirus fusion (F) protein and a mutated hemagglutinin (H) protein of the measles virus (MeV) or the Edmonton strain of the measles virus (MeV_Edm), wherein the cytoplasmic portions of the F and the H protein are truncated, and wherein the amino acids necessary for receptor recognition in the H protein are mutated that it does not interact with CD46, SLAM and/or nectin-4 and further has a single chain antibody to a cell surface marker of hESCs and iPSCs at its ectodomain. In this invention, the single chain variable fragment (scFv) anti-cell surface marker coding sequence of the single chain antibody is fused to the coding sequence at the ectodomain of the H protein, wherein the single chain antibody is selected from the group consisting of CD30, EpCAM (CD326), CD9, Thy-1 (CD90), SSEA-3, SSEA-4, TRA-1-60 or TRA-1-81. The transduction according to the present invention does not interfere with the pluripotency, i.e. present transduced hESCs and iPSCs remain undifferentiated, i.e. are able differentiate into all germ layer lineages.