Abstract:
:Methods for customizing and improving virus vector tropism are limited. In this study, we introduce a microRNA (miRNA)-regulated molecular method to enhance vector transduction without genome alteration. Based on the importance of adenovirus (Ad) vectors for cancer and gene treatment, we exemplified this technology for an Ad type 5 (Ad5) vector temporally carrying a knob from Ad37. We constructed a producer cell line stably expressing a fused Ad5/37 chimeric fiber comprising the Ad5 shaft-tail and the Ad37 knob and a miRNA inhibiting Ad5 knob expression (HEK293-Ad5/37-miRNA). The chimeric Ad5/37 vector resulted in enhanced transduction rates in Ad37 adequately and Ad5 poorly transduced cells. Particularly, encapsidation of the oncolytic Ad5-human telomerase reverse transcriptase (hTERT) vector genome into the chimeric Ad5/37 capsid showed efficient transduction of NK-92 carrier cells. These infected carrier cells then delivered the oncolytic vector to tumor cells, which resulted in enhanced Ad5-hTERT-mediated tumor cell killing. We show that this transiently capsid-modified chimeric vector carrying an Ad5 genome displayed higher transduction efficiencies of natural killer cell-derived NK-92 cells utilized as carriers in cancer immune therapy. In summary, transiently modified adenoviral vectors will have important implications for cancer and gene therapy.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Gao J,Zhang W,Mese K,Bunz O,Lu F,Ehrhardt Adoi
10.1016/j.omtm.2020.06.010subject
Has Abstractpub_date
2020-06-18 00:00:00pages
376-389issn
2329-0501pii
S2329-0501(20)30134-0journal_volume
18pub_type
杂志文章abstract::Gene therapy has been shown to be a feasible approach to treat inherited disorders in vivo. Among the currently used viral vector systems, adeno-associated virus (AAV) vectors are the most advanced and have been applied in patients successfully. An important drawback of non-integrating AAV vectors is their loss of exp...
journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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