Imperial College London, Gene Therapy Research Group, Sir Alexander Fleming Building, National Heart and Lung Institute, South Kensington, London SW7 2AZ, UK.
Expert Opin Biol Ther. 2011 Sep;11(9):1177-91. doi: 10.1517/14712598.2011.582035. Epub 2011 May 9.
The early potential of gene therapy is slowly becoming realized following the recent treatment of patients with severe combined immunodeficiency and ocular diseases. However at present the field of gene therapy is tempered by the toxicity issues, mainly that of the integrated retroviral vector used in most trials which led to oncogenesis in several of the treated patients. The development of safer, alternative vectors is therefore vital for further progress in this field, in particular vectors which remain episomal and are therefore less genotoxic. One such unique class of vectors are those based on scaffold matrix attachment regions (S/MARs) elements, which are maintained extra-chromosomally and replicate in vitro and in vivo.
The overview here describes the most relevant studies utilizing the S/MAR element to episomally modify mammalian cells and tissues with a particular focus on liver tissue, as well as the brain, the muscle, the eye, cancer cells, embryonic cells and neonatal mice. For this purpose, recently published data in these areas (mainly articles published between 2000 and 2010) are reviewed.
The utilisation of vectors harbouring an S/MAR element is an efficient, safe and cost-effective way to episomally modify mammalian cells.
随着最近对严重联合免疫缺陷和眼部疾病患者的治疗，基因治疗的早期潜力正在慢慢实现。然而，目前基因治疗领域受到毒性问题的限制，主要是大多数试验中使用的整合逆转录病毒载体导致了一些治疗患者的癌变。因此，开发更安全、替代的载体对于该领域的进一步发展至关重要，特别是那些保持附加体且因此毒性较低的载体。一类独特的载体是基于支架基质附着区（S/MAR）元件的载体，这些元件在染色体外维持，并在体外和体内复制。
这里的综述描述了利用 S/MAR 元件对哺乳动物细胞和组织进行附加体修饰的最相关研究，特别关注肝脏组织以及大脑、肌肉、眼睛、癌细胞、胚胎细胞和新生小鼠。为此，综述了这些领域最近发表的数据（主要是 2000 年至 2010 年期间发表的文章）。
携带 S/MAR 元件的载体的利用是一种有效、安全且具有成本效益的方法，可以对哺乳动物细胞进行附加体修饰。
