Adenovirus serotype 5 vectors with Tat-PTD modified hexon and serotype 35 fiber show greatly enhanced transduction capacity of primary cell cultures.
Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus-receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
Di
D
Yu
Chuan
C
Jin
Mohanraj
M
Ramachandran
Jing
J
Xu
Berith
B
Nilsson
Olle
O
Korsgren
Katarina
K
Le Blanc
Lene
L
Uhrbom
Karin
K
Forsberg-Nilsson
Bengt
B
Westermark
Rachel
R
Adamson
Norman
N
Maitland
Xiaolong
X
Fan
Magnus
M
Essand
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics*; D002460:Cell Line; D023061:Gene Order; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D061251:Primary Cell Culture; D013601:T-Lymphocytes / Q000276:immunology; D014018:Tissue Distribution; D014161:Transduction, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D036022:Capsid Proteins; C018315:hexon capsid protein, Adenovirus; D054322:tat Gene Products, Human Immunodeficiency Virus