Abstract: Replication-defective lentiviral vectors are described. Using this vector, methods of directing evolution of a target polynucleotide of interest for obtaining variants of the target polynucleotide, methods to generate genetic variability by preparing a cell library, and methods to isolate and/or screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells and to identify theses polynucleotide variants or protein variants responsible for this phenotype are described.

Abstract: A method of directing evolution of a target polynucleotide of interest for obtaining variants of this target polynucleotide, a method to generate genetic variability by preparing a cell library, and a method to isolate or to screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells, and to identify theses polynucleotide variants or protein variants responsible for this phenotype are described.

Abstract: The present invention concerns a method of directing evolution of a target polynucleotide of interest for obtaining variants of this target polynucleotide, as well as a method to generate genetic variability by preparing a cell library. This invention also relates to a method to isolate or to screen variants of a polynucleotide or variants of a protein able to impact the phenotype of a cell or to confer a desired phenotype to target cells, and to identify theses polynucleotide variants or protein variants responsible for this phenotype.

Abstract: A polypeptide having a nucleoside or nucleotide kinase activity, which comprises a wild-type nucleoside or nucleotide kinase mutated at at least one amino acid position within the active site of nucleoside or nucleotide kinase to increase kinase catalytic activity towards a given nucleotide or nucleoside analog compared to the wild-type nucleoside or nucleotide kinase. A polynucleotide coding for said polypeptide. Methods, including therapeutic ones, using said polypeptide and polynucleotide.