CNS gene delivery by retrograde transport of recombinant replication-defective adenoviruses.
The ability to program recombinant gene expression in specific sets of motor and sensory neurons would facilitate the treatment of a number of acquired and inherited central nervous system (CNS) diseases. In this report, we demonstrate that intramuscular injection of replication-defective recombinant adenovirus results in high-level recombinant gene expression, specifically in the CNS motor and sensory neurons that innervate the inoculated muscles. Neural expression of the recombinant genes results from virus transport into the CNS, presumably by retrograde axonal transport. This novel method of neural gene delivery may be of value in studies designed to improve understanding and treatment of inherited and acquired neurological diseases.
Ghadge
G D
GD
Department of Neurology, University of Chicago School of Medicine, IL 60637.
Roos
R P
RP
Kang
U J
UJ
Wollmann
R
R
Fishman
P S
PS
Kalynych
A M
AM
Barr
E
E
Leiden
J M
JM
D000256:Adenoviridae / Q000235:genetics* / Q000302:isolation & purification; D000344:Afferent Pathways; D000818:Animals; D001370:Axonal Transport; D001483:Base Sequence; D001933:Brain Stem / Q000821:virology*; D002552:Cerebral Ventricles / Q000821:virology*; D004274:DNA, Recombinant / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D003673:Defective Viruses / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006614:Hindlimb / Q000294:innervation; D007002:Hypoglossal Nerve / Q000821:virology*; D007273:Injections, Intramuscular; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D009046:Motor Neurons / Q000821:virology; D009132:Muscles / Q000294:innervation / Q000821:virology; D009475:Neurons, Afferent / Q000821:virology; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013116:Spinal Cord / Q000821:virology*; D013979:Tibial Nerve / Q000821:virology*; D014059:Tongue / Q000294:innervation; D014276:Trigeminal Nerve / Q000821:virology; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
D004274:DNA, Recombinant; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D001616:beta-Galactosidase