Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures

作者：Yu, Di; Jin, Chuan; Ramachandran, Mohanraj; Xu, Jing; Nilsson, Berith; Korsgren, Olle; Le Blanc, Katarina; Uhrbom, Lene; For**erg-Nilsson, Karin; Westermark, Bengt; Adamson, Rachel; Maitland, Norman; Fan, Xiaolong; Essand, Magnus^*

来源：PLos One, 2013, 8(1): e54952.

DOI：10.1371/journal.pone.0054952

• VIVO GENE-TRANSFER
• CANCER STEM-CELLS
• ONCOLYTIC ADENOVIRUS
• IN-VIVO
• BINDING ABLATION
• RECOMBINANT ADENOVIRUSES
• RAPID GENERATION
• PROSTATE-CANCER
• TUMOR-CELLS
• CAR-BINDING

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.

• 出版日期2013-1-25
• 单位北京师范大学