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Issue 12, 2013
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Effects of spatial distribution of the nuclear localization sequence on gene transfection in catiomer–gene polyplexes

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Abstract

A spatial effect of targeted signal distribution is found in catiomer–gene polyplexes which strongly influences the gene transfection profiles. The nuclear localization sequence PKKKRKV (NLS) is chosen as the target ligand. For a given gene delivery system of constant composition, size, and charge, it is engineered such that the NLS is the only structural variable in polyplexes. This unique architecture of polyplexes relies on successive electrostatic interaction. The structural features of the PKKKRKV sequence in polyplexes are investigated by NMR. The gene transfection profiles of the polyplexes are found to be well correlated with the spatial distribution of the nuclear localization sequence. Upon modification of nuclear localization, the gene transfection efficiency is found to increase remarkably from 40% to 60%. The drastic improvement of gene transfection is explained by a NLS spatial distribution mechanism. High gene transfection based on spatial NLS distribution provides a new base for the design and development of non-viral gene delivery vectors.

Graphical abstract: Effects of spatial distribution of the nuclear localization sequence on gene transfection in catiomer–gene polyplexes

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Supplementary files

Article information


Submitted
17 Nov 2012
Accepted
25 Jan 2013
First published
25 Jan 2013

J. Mater. Chem. B, 2013,1, 1712-1721
Article type
Paper

Effects of spatial distribution of the nuclear localization sequence on gene transfection in catiomer–gene polyplexes

X. Cai, H. Dong, J. Ma, H. Zhu, W. Wu, M. Chu, Y. Li and D. Shi, J. Mater. Chem. B, 2013, 1, 1712
DOI: 10.1039/C3TB00425B

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