Improved gene delivery into neuroglial cells using a fiber-modified adenovirus vector.
One impediment to treating neuronal diseases is finding ways to introduce genes into specific neuroglial cell types. Here we describe the strategy for efficient gene delivery via transferrin receptor using an adenovirus bearing a peptide mimic for transferrin. The attachment of the peptide consisted of 12 amino acids on the C-terminus of adenovirus fiber protein significantly improved entry and expression of a beta-galactosidase transgene into neuroglial cells such as astrocytes, and Schwann cells. The entry of re-targeted viruses into cells depends on the attached peptide and the transferrin receptor. Furthermore, transferrin did not affect gene delivery by the engineered adenovirus, suggesting that the effectiveness of therapeutic agents targeted to the receptor would not be diminished by competition with the abundant endogenous transferrin present in the plasma. Therefore, such transduction systems hold promise for efficient delivering gene to neuroglial cells in gene therapy protocols.
Joung
Insil
I
Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA.
Harber
Greg
G
Gerecke
Kimberly M
KM
Carroll
Steven L
SL
Collawn
James F
JF
Engler
Jeffrey A
JA
D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000008:administration & dosage*; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009457:Neuroglia / Q000378:metabolism*; D051381:Rats; D011990:Receptors, Transferrin / Q000378:metabolism*; D014161:Transduction, Genetic / Q000379:methods*; D014168:Transferrin / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D004279:DNA, Viral; D011990:Receptors, Transferrin; D014168:Transferrin