A designer biomimetic vector with a chimeric architecture for targeted gene transfer

Yuhua Wang; Sriramchandra Sastry Mangipudi; Brenda F. Canine; Arash Hatefi

doi:10.1016/j.jconrel.2009.03.005

A designer biomimetic vector with a chimeric architecture for targeted gene transfer

Yuhua Wang, Sriramchandra Sastry Mangipudi, Brenda F. Canine, Arash Hatefi

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

Abstract

Designer biomimetic vectors are genetically engineered biomacromolecules that are designed to mimic viral characteristics in order to overcome the cellular barriers associated with the targeted gene transfer. The vector in this study was genetically engineered to contain at precise locations: a) four tandem repeating units of N-terminal domain of histone H2A to condense DNA into stable nanosize particles suitable for cellular uptake, b) a model targeting motif to target HER2 and enhance internalization of nanoparticles, and c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and promote escape of the nanoparticles into the cytosol. The results demonstrate that a fully functional, multi-domain, designer vector can be engineered to target cells with high specificity, overcome the biological barriers associated with targeted gene transfer, and mediate efficient gene transfer.

Original language	English (US)
Pages (from-to)	46-53
Number of pages	8
Journal	Journal of Controlled Release
Volume	137
Issue number	1
DOIs	https://doi.org/10.1016/j.jconrel.2009.03.005
State	Published - Jul 1 2009
Externally published	Yes

All Science Journal Classification (ASJC) codes

Pharmaceutical Science

Keywords

Biomimetic vector
Designer biomacromolecule
Gene therapy
Non-viral vector

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10.1016/j.jconrel.2009.03.005

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abstract = "Designer biomimetic vectors are genetically engineered biomacromolecules that are designed to mimic viral characteristics in order to overcome the cellular barriers associated with the targeted gene transfer. The vector in this study was genetically engineered to contain at precise locations: a) four tandem repeating units of N-terminal domain of histone H2A to condense DNA into stable nanosize particles suitable for cellular uptake, b) a model targeting motif to target HER2 and enhance internalization of nanoparticles, and c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and promote escape of the nanoparticles into the cytosol. The results demonstrate that a fully functional, multi-domain, designer vector can be engineered to target cells with high specificity, overcome the biological barriers associated with targeted gene transfer, and mediate efficient gene transfer.",

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AU - Canine, Brenda F.

AU - Hatefi, Arash

N1 - Funding Information: This work was funded in part by the American Cancer Society (ACS-IRG-77-003-26).

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AB - Designer biomimetic vectors are genetically engineered biomacromolecules that are designed to mimic viral characteristics in order to overcome the cellular barriers associated with the targeted gene transfer. The vector in this study was genetically engineered to contain at precise locations: a) four tandem repeating units of N-terminal domain of histone H2A to condense DNA into stable nanosize particles suitable for cellular uptake, b) a model targeting motif to target HER2 and enhance internalization of nanoparticles, and c) a pH-responsive synthetic fusogenic peptide to disrupt endosome membranes and promote escape of the nanoparticles into the cytosol. The results demonstrate that a fully functional, multi-domain, designer vector can be engineered to target cells with high specificity, overcome the biological barriers associated with targeted gene transfer, and mediate efficient gene transfer.

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KW - Non-viral vector

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A designer biomimetic vector with a chimeric architecture for targeted gene transfer

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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