In utero gene transfer to the mouse nervous system.
The cellular and molecular environment present in the fetus and early newborn provides an excellent opportunity for effective gene transfer. Innate and pre-existing anti-vector immunity may be attenuated or absent and the adaptive immune system predisposed to tolerance towards xenoproteins. Stem cell and progenitor cell populations are abundant, active and accessible. In addition, for treatment of early lethal genetic diseases of the nervous system, the overarching advantage may be that early gene supplementation prevents the onset of irreversible pathological changes. Gene transfer to the fetal mouse nervous system was achieved, albeit inefficiently, as far back as the mid-1980s. Recently, improvements in vector design and production have culminated in near-complete correction of a mouse model of spinal muscular atrophy. In the present article, we review perinatal gene transfer from both a therapeutic and technological perspective.
Institute for Women's Health, University College London, 86-96 Chenies Mews, London WC1E 6HX, UK.
Ahad A
AA
Rahim
Andrew M S
AM
Wong
Suzanne M K
SM
Buckley
Jerry K Y
JK
Chan
Anna L
AL
David
Jonathan D
JD
Cooper
Charles
C
Coutelle
Donald M
DM
Peebles
Simon N
SN
Waddington
D000818:Animals; D005260:Female; D005333:Fetus / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000201:enzymology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D009420:Nervous System; D011247:Pregnancy