VikAD, a Vika site-specific recombinase-based system for efficient and scalable helper-dependent adenovirus production

Stacia Phillips; Paula Valino Ramos; Priyadharishini Veeraraghavan; Samuel M Young

doi:10.1016/j.omtm.2021.12.001

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VikAD, a Vika site-specific recombinase-based system for efficient and scalable helper-dependent adenovirus production

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VikAD, a Vika site-specific recombinase-based system for efficient and scalable helper-dependent adenovirus production

Stacia Phillips, Paula Valino Ramos, Priyadharishini Veeraraghavan and Samuel M Young

Molecular therapy. Methods & clinical development, Vol.24, pp.117-126

12/2021

DOI: 10.1016/j.omtm.2021.12.001

PMCID: PMC8718833

PMID: 35024378

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Abstract

Recombinant viral vectors have become integral tools for basic in vivo research applications. Helper-dependent adenoviral (HdAd) vectors have a large packaging capacity of ∼36 kb of DNA that mediate long-term transgene expression in vitro and in vivo. The large carrying capacity of HdAd enables basic research or clinical applications requiring the delivery of large genes or multiple transgenes which cannot be packaged into other widely-used viral vectors. Currently, common HdAd production systems use a helper Ad virus (HV) with a packaging signal (Ψ) that is flanked by either loxP or FRT sites, which is excised in producer cells expressing Cre or Flp recombinases to prevent HV packaging. However, these production systems prevent the use of HdAd vectors for genetic strategies that rely on Cre or Flp recombination for cell-type specific expression. To overcome these limitations, we developed the VikAD production system, which is based on producer cells expressing the Vika recombinase and a HV that contains a Ψ flanked by vox sites. The availability of this production system will greatly expand the utility and flexibility of HdAd vectors for use in research applications to monitor and manipulate cellular activity with increased specificity. [Display omitted] VikAD is a Helper-Dependent Adenovirus (HdAd) production platform that utilizes a cell line expressing the Vika site-specific recombinase and an Ad Helper Virus that contains the packaging sequence flanked by vox sites. VikAD enables use of HdAd with genetic intersectional strategies using Cre and Flp or other site-specific recombinases.

Details

Title: Subtitle: VikAD, a Vika site-specific recombinase-based system for efficient and scalable helper-dependent adenovirus production
Creators: Stacia Phillips - Department of Anatomy and Cell Biology
Paula Valino Ramos - Department of Anatomy and Cell Biology
Priyadharishini Veeraraghavan - Department of Anatomy and Cell Biology
Samuel M Young - Department of Anatomy and Cell Biology
Resource Type: Journal article
Publication Details: Molecular therapy. Methods & clinical development, Vol.24, pp.117-126
DOI: 10.1016/j.omtm.2021.12.001
PMID: 35024378
PMCID: PMC8718833
NLM abbreviation: Mol Ther Methods Clin Dev
ISSN: 2329-0501
eISSN: 2329-0501
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/100000055, name: National Institute on Deafness and Other Communication Disorders; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke; DOI: 10.13039/100008893, name: University of Iowa
Language: English
Date published: 12/2021
Academic Unit: Microbiology and Immunology; Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
Record Identifier: 9984201784002771

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