Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus.
Choroideremia (CHM) is an X-linked retinal degenerative disease resulting from a lack of functional Rab Escort Protein-1 (REP-1). As a first step in developing gene-based therapies for this disease, we evaluated the feasibility of delivering functional REP-1 to defective lymphocytes and fibroblasts isolated from individuals with CHM. A recombinant adenovirus delivering the full-length human cDNA encoding REP-1 under the control of a cytomegalovirus promoter was generated. Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo.
Anand
Vibha
V
Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6069, USA. jebennet@mail.med.upenn.edu
Barral
Duarte C
DC
Zeng
Yong
Y
Brunsmann
Frank
F
Maguire
Albert M
AM
Seabra
Miguel C
MC
Bennett
Jean
J
D048868:Adaptor Proteins, Signal Transducing; D000256:Adenoviridae / Q000235:genetics; D019883:Alkyl and Aryl Transferases; D002478:Cells, Cultured; D015794:Choroideremia / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D018076:DNA, Complementary / Q000235:genetics; D005240:Feasibility Studies; D005347:Fibroblasts / Q000378:metabolism; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C081787:CHM protein, human; D018076:DNA, Complementary; D019883:Alkyl and Aryl Transferases; D020691:rab GTP-Binding Proteins