Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches.
Gene therapy for mucopolysaccharidoses: in vivo and ex vivo approaches.
复制标题
DOI：
10.1186/s13052-018-0565-y
复制
发表时间：
2018-11-16
影响因子：
3.6
通讯作者：
Bernardo ME
中科院分区：
文献类型：
--
作者：
Fraldi A;Serafini M;Sorrentino NC;Gentner B;Aiuti A;Bernardo ME
粘多糖(MPS)是一组溶酶体储存障碍，由溶酶体酶缺乏催化糖胺多聚糖(GAG)的逐步降解引起。目前的治疗策略有酶替代疗法和异基因造血干细胞移植的报道，以减少患者的发病率和改善他们的生活质量，但它们与残留疾病负担的持久性有关，特别是在神经认知和肌肉骨骼水平上。这表明需要更有效的治疗方法，能够有效和快速地将酶输送到受影响的器官，特别是大脑和骨骼。与传统方法相比，旨在纠正患者细胞中遗传缺陷的基因治疗(GT)策略可能代表着对MPS治疗的重大改进。虽然体内GT策略预见了将病毒载体颗粒直接给患者，目的是为受影响的细胞提供正常的互补DNA，但体外GT方法是基于患者细胞的体外转导，这些细胞随后被回输。这篇综述提供了对在体内和体外基于GT的方法在MPS中所取得的最新成就的洞察，并对医学界的未来进行了展望。
Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by a deficiency in lysosomal enzymes catalyzing the stepwise degradation of glycosaminoglycans (GAGs). The current therapeutic strategies of enzyme replacement therapy and allogeneic hematopoietic stem cell transplantation have been reported to reduce patient morbidity and to improve their quality of life, but they are associated with persistence of residual disease burden, in particular at the neurocognitive and musculoskeletal levels. This indicates the need for more efficacious treatments capable of effective and rapid enzyme delivery to the affected organs, especially the brain and the skeleton. Gene therapy (GT) strategies aimed at correcting the genetic defect in patient cells could represent a significant improvement for the treatment of MPS when compared with conventional approaches. While in-vivo GT strategies foresee the administration of viral vector particles directly to patients with the aim of providing normal complementary DNA to the affected cells, ex-vivo GT approaches are based on the ex-vivo transduction of patient cells that are subsequently infused back. This review provides insights into the state-of-art accomplishments made with in vivo and ex vivo GT-based approaches in MPS and provide a vision for the future in the medical community.
登录
查看更多内容
影响因子：
12.4
作者：
Cotugno, Gabriella;Annunziata, Patrizia;Auricchio, Alberto
通讯作者：
Auricchio, Alberto
影响因子：
3.8
作者：
Fox, Joyce E.;Volpe, Linda;Sly, William S.
通讯作者：
Sly, William S.
影响因子：
5.1
作者：
Hopkins, Patrick V.;Campbell, Carlene;Kiesling, Jami
通讯作者：
Kiesling, Jami
影响因子：
3.5
作者：
Fu, Haiyan;DiRosario, Julianne;McCarty, Douglas M.
通讯作者：
McCarty, Douglas M.
影响因子：
5.3
作者：
Cressant, A;Desmaris, N;Heard, JM
通讯作者：
Heard, JM