Fetal somatic gene therapy.
Fetal somatic gene therapy is emerging as a new experimental approach, in particular to prevent irreversible perinatal disease manifestation for many inherited conditions. Early therapeutic gene application may also allow targeting of still expanding stem cell populations of organ or cell systems inaccessible later in life and help to avoid immune sensitization against the therapeutic vector system or transgene protein product. The progress in development of ultrasound scanning and embryofetoscopy over the last decade has made minimally invasive administration of therapeutic gene transfer vectors to the fetus in utero possible in principle. We review here the different considerations in choosing candidate diseases, the possible routes of administration and times in fetal development for application of a therapeutic gene and discuss the benefits and problems of present vector systems in this context. Given the many unknown aspects of fetal gene transfer, it is essential to extensively investigate this new approach to gene therapy in animal models for specific diseases, to improve on the technology of delivery and to assess efficacy of expression as well as the possible side effects before application to humans can be considered.
Douar
A M
AM
Department of Biochemistry and Molecular Genetics, Imperial College, School of Medicine at St. Mary's, London, UK.
Themis
M
M
Coutelle
C
C
D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000628:therapy; D000818:Animals; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D005260:Female; D005315:Fetal Diseases / Q000235:genetics / Q000628:therapy*; D030342:Genetic Diseases, Inborn / Q000235:genetics / Q000628:therapy*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007107:Immune System / Q000196:embryology; D008297:Male; D009136:Muscular Dystrophies / Q000235:genetics / Q000628:therapy; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D020163:Ornithine Carbamoyltransferase Deficiency Disease; D011247:Pregnancy; D012190:Retroviridae / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000628:therapy
D004247:DNA; D009954:Ornithine Carbamoyltransferase; D000243:Adenosine Deaminase