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Development of magnetic nanoparticle (MNP) based delivery system for gene transfer to multipotent neural precursor cells (NPCs)

开发基于磁性纳米颗粒（MNP）的递送系统，用于将基因转移至多能神经前体细胞（NPC）

基本信息

批准号：
BB/F013884/1
负责人：
Divya Chari
金额：
$ 45.24万
依托单位：
Keele University
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF013884%2F1
关键词：
Development magnetic nanoparticle MNP based

项目摘要

The adult brain and spinal cord (together called the central nervous system or CNS) have a poor capacity to repair after injury. This leads to a poor prognosis for patients with severe spinal cord injuries and devastating consequences for their quality of life. Neural precursor cells or NPCs, have an enormous potential for increasing repair at injury sites in the CNS. As NPCs have the ability to migrate into areas of damage in the nervous system, an important application for these cells is as cellular vehicles to transport therapeutic genes (and other molecules) to the sites of injury in the CNS. Currently, the most widely used method of delivering genes to NPCs is to use modified viruses carrying genes, which infect cells and then transfer genes into the infected cells. However, this method has a number of drawbacks and is associated with major safety issues. New delivery systems using magnetic nanoparticles (MNPs) could be very useful in this regard, and have many benefits for delivery of genes. MNPs can be coated with genes and are taken up into cells. As they are magnetic,cells carrying MNPs can be targeted to particular areas of damage in the body by placing external magnetic fields over injury sites.Preliminary clinical trials shown that injecting MNPs into the body appears to be safe and do not seem to have toxic or carcinogenic effects. This study will establish if it is possible to use MNPs to deliver therapeutic genes to NPCs (that will then be used for transplantation into the spinal cord). We will assess methods to optimise the uptake of MNPs coated with genes into NPCs and establish if this procedure has any adverse effects on the survival and development of the cells.

成年人的大脑和脊髓(统称为中枢神经系统或CNS)在受伤后修复能力较差。这导致严重脊髓损伤患者的预后很差，并对他们的生活质量造成毁灭性的后果。神经前体细胞在增加中枢神经系统损伤部位的修复方面具有巨大的潜力。由于神经干细胞具有迁移到神经系统损伤区域的能力，这些细胞的一个重要应用是作为细胞载体将治疗基因(和其他分子)运送到中枢神经系统的损伤部位。目前，最广泛使用的向鼻咽癌细胞输送基因的方法是使用携带基因的改良病毒，这种病毒感染细胞，然后将基因转移到受感染的细胞中。然而，这种方法有许多缺点，并与重大安全问题相关。使用磁性纳米颗粒(MNPs)的新型递送系统在这方面可能非常有用，并且在递送基因方面有许多好处。MNPs可以包裹有基因，并被吸收到细胞中。由于携带MNPs的细胞具有磁性，通过在损伤部位施加外部磁场，携带MNPs的细胞可以针对特定的损伤区域。初步临床试验表明，将MNPs注射到体内似乎是安全的，似乎没有毒性或致癌作用。这项研究将确定是否有可能使用MNPs将治疗性基因输送到NPC(然后将用于移植到脊髓中)。我们将评估优化将包裹着基因的MNPs吸收到NPC中的方法，并确定这一过程是否对细胞的生存和发育有任何不利影响。