Journal
CELLULAR AND MOLECULAR BIOENGINEERING
Volume 7, Issue 3, Pages 334-343Publisher
SPRINGER
DOI: 10.1007/s12195-014-0334-y
Keywords
Adeno-associated virus; Gene delivery; Matrix metalloproteinase; Mosaic capsid
Funding
- National Science Foundation [0955536]
- Cancer Prevention Research Institute of Texas [RP130455]
- American Heart Association [13GRNT14420044]
- Direct For Mathematical & Physical Scien
- Division Of Materials Research [0955536] Funding Source: National Science Foundation
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Virus nanonodes, a tunable multi-input protease-responsive gene delivery platform, was recently built by exploiting the self-assembly property of adeno-associated virus capsids. Upon detection of specific inputs (e.g., matrix metalloproteinases-MMPs), the engineered viruses output gene delivery to targeted cells. The first generation protease-activatable viruses (PAVs) displayed the desired protease-activated cellular receptor binding and transduction behaviors. However, the less than wild type (WT) level of gene delivery achieved by the prototype viruses has left room for improvement. In this report, we have devised a method to tackle this efficiency problem. Specifically, by controlling the ratio of WT to protease-activatable subunits in the assembled 60-mer virus capsid, we can easily increase the level of overall transduction achieved by the PAVs. Since a number of MMPs are overexpressed in a vast range of human pathologies, including cancer and cardiovascular disease, the protease-sensing viruses may find broad clinical use in future gene therapy applications.
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