VIRAL VECTORS HAVING TISSUE TROPISM FOR T-LYMPHOCYTES, B- AND MAST CELLS

摘要

The present invention relates to a method of introducing an expressible non-viral nucleic acid sequence into a cell having a common non-universal binding receptor and selected from T lymphocytes, B-, and mast cells, comprising contacting said cell with a viral vector comprising a recombinant nucleic acid sequence containing sequence for said expressible non-viral nucleic acid and comprising a modified viral coat consisting of native viral coat proteins and modified coat protein containing adenoviral amino acid sequence from an adenoviral serotype 35 or 51 fibre protein, wherein said adenoviral sequence of said modified protein is a ligand for said binding receptor. Alternatively said vector comprises a sequence coding for a viral capsid consisting of native adenoviral capsid proteins and modified capsid protein containing amino acid sequence from an adenoviral serotype other than the serotype of said native capsid proteins, wherein said modified protein is a ligand for said binding receptor. The present invention also relates to a method for transducing a cell, said cell selected from the group consisting of T lymphocytes, B cells, and mast cells comprising contacting said cells with an adenovirus particle comprising a non-adenovirus nucleic acid sequence and a chimeric capsid protein comprising amino acid sequence derived from at least two adenovirus serotypes, wherein said particle has a greater tropism for said cells relative to at least one of the adenovirus serotypes comprising said chimeric capsid protein. The present invention further relates to transduced cells, arrays of subpopulations of cells, a method for ex vivo transduction of a population of cells comprising and a method of administering to a human or other mammalian animal subject a population of cells genetically modified ex vivo. The present invention further relates to a method for identifying the function of a first nucleic acid in hematopoietic cells.