Polyornithine-based polyplexes to boost effective gene silencing in CNS disorders

被引：14

作者：

Conejos-Sanchez, I. ^{[1
,2
,3
]}

Gallon, E. ^{[1
]}

Nino-Pariente, A. ^{[1
]}

Smith, J. A. ^{[2
,3
,5
]}

De la Fuente, A. G. ^{[2
,3
,4
]}

Di Canio, L. ^{[2
,3
,4
]}

Pluchino, S. ^{[2
,3
]}

Franklin, R. J. M. ^{[2
,3
,4
]}

Vicent, M. J. ^{[1
]}

机构：

[1] Ctr Invest Principe Felipe, Polymer Therapeut Lab, C Eduardo Primo Yufera 3, Valencia 46012, Spain

[2] Univ Cambridge, Dept Clin Neurosci, Clifford Allbutt Bldg,Cambridge Biosci Campus, Cambridge, England

[3] Univ Cambridge, NIHR Biomed Res Ctr, Clifford Allbutt Bldg,Cambridge Biosci Campus, Cambridge, England

[4] Univ Cambridge, Wellcome Med Res Council, Jeffrey Cheah Biomed Ctr, Cambridge Stem Cell Inst, Cambridge CB2 0AW, England

[5] Cambridge Innovat Technol Consulting CITC Ltd, St Johns Innovat Ctr, Cowley Rd, Cambridge CB4 0WS, England

来源：

NANOSCALE | 2020年 / 12卷 / 11期

基金：

英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

DEATH RECEPTOR 6; CIRCULAR-DICHROISM; SIRNA DELIVERY; PACLITAXEL POLIGLUMEX; CELL DIFFERENTIATION; NUCLEIC-ACIDS; PLASMID DNA; IN-VITRO; BINDING; GENERATION;

D O I：

10.1039/c9nr06187h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Gene silencing therapies have successfully suppressed the translation of target proteins, a strategy that holds great promise for the treatment of central nervous system (CNS) disorders. Advances in the current knowledge on multimolecular delivery vehicles are concentrated on overcoming the difficulties in delivery of small interfering (si)RNA to target tissues, which include anatomical accessibility, slow diffusion, safety concerns, and the requirement for specific cell uptake within the unique environment of the CNS. The present work addressed these challenges through the implementation of polyornithine derivatives in the construction of polyplexes used as non-viral siRNA delivery vectors. Physicochemical and biological characterization revealed biodegradability and biocompatibility of our polyornithine-based system and the ability to silence gene expression in primary oligodendrocyte progenitor cells (OPCs) effectively. In summary, the well-defined properties and neurological compatibility of this polypeptide-based platform highlight its potential utility in the treatment of CNS disorders.

引用

页码：6285 / 6299

页数：15

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