title: Efficient c-kit receptor-targeted gene transfer to primary human CD34-selected hematopoietic stem cells.
abstract: We have previously reported effective gene transfer with a targeted molecular conjugate adenovirus vector through the c-kit receptor in hematopoietic progenitor cell lines. However, a c-kit-targeted recombinant retroviral vector failed to transduce cells, indicating the existence of significant differences for c-kit target gene transfer between these two viruses. Here we demonstrate that conjugation of an adenovirus to a c-kit-retargeted retrovirus vector enables retroviral transduction. This finding suggests the requirement of endosomalysis for successful c-kit-targeted gene transfer. Furthermore, we show efficient gene transfer to, and high transgene expression (66%) in, CD34-selected, c-kit(+) human peripheral blood stem cells using a c-kit-targeted adenovirus vector. These findings may have important implications for future vector development in c-kit-targeted stem cell gene transfer.
authors.affiliation: Gene Therapy Program, Louisiana State University Health Sciences Center of New Orleans, Louisiana 70112, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhong
authors.forename: P
authors.initials: P
authors.lastname: Oliver
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.forename: D
authors.initials: D
authors.lastname: Good
authors.forename: V
authors.initials: V
authors.lastname: La Russa
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: J R
authors.initials: JR
authors.lastname: Cork
authors.forename: R W
authors.initials: RW
authors.lastname: Veith
authors.forename: C
authors.initials: C
authors.lastname: Theodossiou
authors.forename: J K
authors.initials: JK
authors.lastname: Kolls
authors.forename: P
authors.initials: P
authors.lastname: Schwarzenberger
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D018952:Antigens, CD34 / Q000032:analysis*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D005822:Genetic Vectors; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D011991:Receptors, Virus / Q000032:analysis; D012190:Retroviridae / Q000235:genetics
chemical_list: D018952:Antigens, CD34; C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D019009:Proto-Oncogene Proteins c-kit