Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury

JOURNAL OF CONTROLLED RELEASE

卷:197

Article

Hayakawa, Kentaro^1,2  Uchida, Satoshi³  Ogata, Toru¹  Tanaka, Sakae²  Kataoka, Kazunori^3,4  Itaka, Keiji^2,3 

[1] Natl Rehabil Ctr Persons Disabil, Res Inst, Dept Rehabil Movement Funct, Saitama, Japan

[2] Univ Tokyo, Fac Med, Tokyo 113, Japan

[3] Univ Tokyo, Grad Sch Med, Ctr Dis Biol & Integrat Med, Lab Clin Biotechnol, Tokyo, Japan

[4] Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Tokyo, Japan

关键词: Spinal cord injury;    Brain-derived neurotrophic factor (BDNF);    Gene delivery;    Polyplex;    Intrathecal injection;   

DOI  :  10.1016/j.jconrel.2014.10.027

来源: Elsevier

【 摘 要 】

Spinal cord injury (SCI) is a serious clinical problem that suddenly deprives patients of neurologic function and drastically diminishes their quality of life. Gene introduction has the potential to be effective for various pathological states of SCI because various proteins can be produced just by modifying nucleic acid sequences. In addition, the sustainable protein expression allows to maintain its concentration at an effective level at the target site in the spinal cord. Here we propose an approach using a polyplex system composed of plasmid DNA (pDNA) and a cationic polymer, poly{N'-[N-(2-aminoethyl)-2-aminoethyl] aspartamide} [PAsp(DET)], that has high capacity to promote endosome escape and the long-term safety by self-catalytically degrading within a few days. We applied brain-derived neurotrophic factor (BDNF)-expressing pDNA for SCI treatment by intrathecal injection of PAsp(DET)/pDNA polyplex. A single administration of polyplex for experimental SCI provided sufficient therapeutic effects including prevention of neural cell death and enhancement of motor function recovery. This lasted for a few weeks after SCI, demonstrating the capability of this system to express BDNF in a safe and responsible manner for treatment of various pathological states in SCI. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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