Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency Export

@article{citeulike:5944402, abstract = {The objective of this study was to evaluate the effect of vector architecture on DNA condensation, particle stability, and gene transfer efficiency. Two recombinant non-viral vectors with the same amino acid compositions but different architectures, composed of lysine-histidine (KH) repeating units fused to fibroblast growth factor, were genetically engineered. In one vector lysine residues were dispersed (KHKHKHKHKK) 6 -FGF2, whereas in the other they were in clusters (KKKHHHHKKK) 6 -FGF2. Organization of lysine residues in this manner was inspired by the sequence of DNA condensing motifs that exist in nature (e.g., histones) where lysine residues are organized in clusters. These two constructs were compared in terms of DNA condensation and gene transfer efficiency. It was observed that the construct with KH units in clusters was able to condense pDNA into more stable particles with sizes < 150 nm making them suitable for cellular uptake via receptor mediated endocytosis. This in turn resulted in five times higher transfection efficiency for the cKH-FGF2. This study demonstrates that in targeted non-viral gene transfer, the vector architecture plays as significant a role as its amino acid sequence. Thus, in the design of the non-viral vectors (synthetic or recombinant) this factor should be considered of paramount importance.}, author = {Canine, B. and Wang, Y. and Hatefi, A.}, citeulike-article-id = {5944402}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.jconrel.2008.04.012}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S0168365908001892}, day = {14}, doi = {10.1016/j.jconrel.2008.04.012}, issn = {01683659}, journal = {Journal of Controlled Release}, keywords = {architecture, delivery, gene, lysine-histidine, non-viral, targeted, therapy, vector}, month = {July}, number = {2}, pages = {117--123}, posted-at = {2009-10-15 15:59:22}, priority = {4}, title = {Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency}, url = {http://dx.doi.org/10.1016/j.jconrel.2008.04.012}, volume = {129}, year = {2008} }

TY - JOUR ID - citeulike:5944402 L3 - citeulike-article-id:5944402 N2 - The objective of this study was to evaluate the effect of vector architecture on DNA condensation, particle stability, and gene transfer efficiency. Two recombinant non-viral vectors with the same amino acid compositions but different architectures, composed of lysine-histidine (KH) repeating units fused to fibroblast growth factor, were genetically engineered. In one vector lysine residues were dispersed (KHKHKHKHKK) 6 -FGF2, whereas in the other they were in clusters (KKKHHHHKKK) 6 -FGF2. Organization of lysine residues in this manner was inspired by the sequence of DNA condensing motifs that exist in nature (e.g., histones) where lysine residues are organized in clusters. These two constructs were compared in terms of DNA condensation and gene transfer efficiency. It was observed that the construct with KH units in clusters was able to condense pDNA into more stable particles with sizes < 150 nm making them suitable for cellular uptake via receptor mediated endocytosis. This in turn resulted in five times higher transfection efficiency for the cKH-FGF2. This study demonstrates that in targeted non-viral gene transfer, the vector architecture plays as significant a role as its amino acid sequence. Thus, in the design of the non-viral vectors (synthetic or recombinant) this factor should be considered of paramount importance. IS - 2 JF - Journal of Controlled Release SN - 01683659 EP - 123 TI - Evaluation of the effect of vector architecture on DNA condensation and gene transfer efficiency VL - 129 SP - 117 KW - architecture KW - delivery KW - gene KW - lysine-histidine KW - non-viral KW - targeted KW - therapy KW - vector AU - Canine, B AU - Wang, Y AU - Hatefi, A PY - 2008/07/14/ UR - http://dx.doi.org/10.1016/j.jconrel.2008.04.012 ER -