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Bio-inspired polymer envelopes around adenoviral vectors to reduce immunogenicity and improve in vivo kinetics

Paper ID Volume ID Publish Year Pages File Format Full-Text
176 12 2016 12 PDF Available
Title
Bio-inspired polymer envelopes around adenoviral vectors to reduce immunogenicity and improve in vivo kinetics
Abstract

Adenoviral vectors have attracted substantial interest for systemic tumor gene therapy, but further work is needed to reduce their immunogenicity and alter their biodistribution before they can be used in the clinic. Here we describe a bio-inspired, cleavable PEGylated β-cyclodextrin-polyethyleneimine conjugate (CDPCP) that spontaneously coats adenovirus in solution. This cleavable PEG coating reduces the innate and adaptive immunogenicity of adenovirus particles, as well as improves their biodistribution away from the liver and into the tumor. Insertion of a matrix metalloproteinase substrate sequence into the conjugate allows PEG cleavage at the tumor site, simultaneously reducing liver biodistribution and increasing transgene expression in tumors, thereby avoiding the “PEG dilemma”. Cationic β-cyclodextrin–PEI not only provides electrostatic attraction to promote envelope attachment to the viral capsid, but it also improves vector internalization and transduction after PEG cleavage. These results suggest that CDPCP may help expand the use of adenoviral vectors in cancer gene therapy.Statement of significanceThe synthesized β-cyclodextrin–PEI-MMP-cleavable-PEG polymer (CDPCP), held great potential for gene therapy when applied for adenovirus coating. The β-cyclodextrin–PEI provided a powerful electrostatic attraction to attach the whole polymer onto the viral capsid, while the MMPs-cleavable PEG reduced innate and adaptive immunogenicity and improved the biodistribution of adenovirus vectors due to the tumor-specific enzyme triggered PEG cleavage. More importantly, an ingenious cooperation between the two components could solve the PEG dilemma. The CDPCP/Ad complexes exhibited a comprehensive and valued profile to be a candidate vector for future tumor gene therapy, we believe the current investigation on this kind of biomaterial may be of particular interest to the readership of Acta biomaterialia.

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Keywords
Adenovirus; Cleavable PEG; β-Cyclodextrin; PEI; Gene therapy
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Bio-inspired polymer envelopes around adenoviral vectors to reduce immunogenicity and improve in vivo kinetics
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Publisher
Database: Elsevier - ScienceDirect
Journal: Acta Biomaterialia - Volume 30, 15 January 2016, Pages 94–105
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us