TY - JOUR
T1 - A designer biomimetic vector with a chimeric architecture for targeted gene transfer
AU - Wang, Yuhua
AU - Mangipudi, Sriramchandra Sastry
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).
PY - 2009/7/1
Y1 - 2009/7/1
N2 - 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.
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.
KW - Biomimetic vector
KW - Designer biomacromolecule
KW - Gene therapy
KW - Non-viral vector
UR - http://www.scopus.com/inward/record.url?scp=67349150011&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349150011&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2009.03.005
DO - 10.1016/j.jconrel.2009.03.005
M3 - Article
C2 - 19303038
AN - SCOPUS:67349150011
SN - 0168-3659
VL - 137
SP - 46
EP - 53
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -