Ivan Kempson - Controlled delivery of recombinant adeno-associated virus serotype 2 using pH-sensitive poly(ethylene glycol)-poly-L-histidine hydrogels

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      Publication Details (including relevant citation   information):

      Yi-Fang Zeng, S.-Ja Tseng, Ivan M. Kempson, Shu-Fen Peng,   Wen-Teng Wu, Je-Ruei Liu, Controlled delivery of recombinant   adeno-associated virus serotype 2 using pH-sensitive   poly(ethylene glycol)-poly-L-histidine hydrogels, Biomaterials,

      33 (2012) 9239-9245


      Loading of viral vectors in synthetic polymers is a promising   strategy for overcoming hurdles associated with viral gene   delivery. For enhanced gene expression at a specific site, gene   transfer by using hydrogels represents a versatile approach. In   this study, adeno-associated virus serotype 2 containing the   green fluorescent protein gene (rAAV2-GFP) were loaded into   poly(ethylene glycol) (PEG) hydrogels, with and without   incorporation of poly-L-hisditine (polyHis). Inclusion of polyHis   created pH responsive hydrogels in a physiological range of   tissues, containing the damaged vasculature and activated   phagocytosis. The fraction of polyHis used controlled the degree   of swelling, water uptake and subsequent degradation of the   hydrogels and release rate of rAAV2-GFP. The swelling ratio of   the PEG-polyHis hydrogels increased inversely with environment   pH. As pH declined from 7.4 to 6.0, PEG-polyHis hydrogel swelling   ratio and degradation rate increased 875% and 135%, respectively.   As a result, release and transduction efficiency of the rAAV2-GFP   from PEG-polyHis hydrogel in human HT-1080 fibrosarcoma cells   increased significantly compared to a PEG hydrogel. Transduction   rate can be controlled by the hydrogels’ polyHis concentration   and is sensitive to localized decreases in pH consistent with   inflammation. This is relevant to optimizing parameters for wound   care and regenerative medicine applications.

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