02799nas a2200313   4500008004100000022001400041245014200055210006900197260007100266300001400337490000700351520168200358653003002040653001602070653002602086653002102112653001702133100001602150700002502166700002002191700002102211700001902232700001702251700002102268700002602289700002402315700001902339856012702358       2016                        eng d  a1543-838400aEfficient cellular entry of (r-x-r)-type carbamate-plasmid DNA complexes and its implication for noninvasive topical DNA delivery to skin0 aEfficient cellular entry of rxrtype carbamateplasmid DNA complex  a1155 16TH ST, NW, WASHINGTON, DC 20036 USAbAMER CHEMICAL SOCcJUN  a1779-17900 v133 a<p>Arginine-rich cell penetrating peptides are powerful tools for in vitro as well as in vivo delivery of a wide plethora of biomolecules. However, presence of consecutive arginine residues leads to enhanced amenability for proteolytic degradation as well as steric hindrances for membrane interactions which compromise its bioavailability. In order to overcome these limitations we previously reported a safe and stable octaarginine based oligomer, i.e., (r-x-r)4-carbamate, where the backbone amide linkages were replaced by carbamate linkages and 6-aminohexanoic acid based spacer moieties were incorporated for better flexibility, hydrophobicity, optimal spacing of guanidinium groups, and protection against proteolytic cleavage; resulting in improved transfection efficiency over its amide counterpart. In the present work we have investigated the mechanism behind this enhanced transfection efficiency and, based on our observations, demonstrate how the synergistic effect of rationalized oligomer designing, complex characteristics, and cell type contributes to overall effective intracellular delivery. Our results indicate that the (r-x-r)4-carbamate plasmid DNA complexes primarily utilize lipid raft dependent pathway of cellular entry more than other pathways, and this possibly facilitates their increased entry in the lipid raft rich milieu of skin cells. We also emphasize the utility of oligomer (r-x-r)4-carbamate as an efficient carrier for topical delivery of nucleic acids in skin tissue. This carrier can be utilized for safe, efficient, and noninvasive delivery of therapeutically relevant macromolecular hydrophilic cargo like nucleic acids to skin.</p>10aCell penetrating peptides10aendocytosis10anucleic acid delivery10askin penetration10atransfection1 aVij, Manika1 aNatarajan, Poornemaa1 aYadav, Amit, K.1 aPatil, Kiran, M.1 aPandey, Tanuja1 aGupta, Nidhi1 aSanthiya, Deenan1 aKumar, Vaijayanti, A.1 aFernandes, Moneesha1 aGanguli, Munia  uhttps://library.ncl.res.in/content/efficient-cellular-entry-r-x-r-type-carbamate-plasmid-dna-complexes-and-its-implication