Targeted retroviral transduction of c-kit+ hematopoietic cells using novel ligand display technology.
Gene therapy for a wide variety of disorders would be greatly enhanced by the development of vectors that could be targeted for gene delivery to specific populations of cells. We describe here high-efficiency targeted transduction based on a novel targeting strategy that exploits the ability of retroviruses to incorporate host cell proteins into the surface of the viral particle as they bud through the plasma membrane. Ecotropic retroviral particles produced in cells engineered to express the membrane-bound form of stem cell factor (mbSCF) transduce both human cell lines and primary cells with high efficiency in a strictly c-kit (SCF receptor)-dependent fashion. The availability of efficient targeted vectors provides a platform for the development of a new generation of therapies using in vivo gene delivery.
Chandrashekran
Anil
A
Department of Haematology, Faculty of Medicine, Imperial College London, Hammersmith Hospital Campus, Du Cane Rd, London W12 0NN, United Kingdom.
Gordon
Myrtle Y
MY
Casimir
Colin
C
D036022:Capsid Proteins; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D015202:Protein Engineering; D019009:Proto-Oncogene Proteins c-kit; D012190:Retroviridae / Q000235:genetics*; D019089:Stem Cell Factor; D014161:Transduction, Genetic / Q000379:methods*; D019065:Virus Assembly
D036022:Capsid Proteins; D008024:Ligands; D019089:Stem Cell Factor; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit