A designer biomimetic vector with a chimeric architecture for targeted gene transfer.
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.
Wang
Yuhua
Y
Department of Pharmaceutical Sciences, Center for Integrated Biotechnology, Washington State University, P.O. Box 646534, Pullman, WA 99164, USA.
Mangipudi
Sriramchandra Sastry
SS
Canine
Brenda F
BF
Hatefi
Arash
A
D000818:Animals; D032701:Biomimetics; D002470:Cell Survival / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D011992:Endosomes / Q000235:genetics; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D008561:Membrane Fusion; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles; D010316:Particle Size; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012680:Sensitivity and Specificity; D020080:Tandem Repeat Sequences / Q000235:genetics
D002738:Chloroquine; D004247:DNA; D049452:Green Fluorescent Proteins; D006657:Histones; D018942:Macrolides; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; C485184:enhanced green fluorescent protein; C066951:GALA peptide; C040929:bafilomycin A1