Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology.
Therapeutic strategies for autism: targeting three levels of the central dogma of molecular biology.
复制标题
DOI：
10.1038/s41398-023-02356-y
复制
发表时间：
2023-02-16
影响因子：
6.8
通讯作者：
Iakoucheva, Lilia M.
中科院分区：
文献类型：
--
作者：
Hong, Derek;Iakoucheva, Lilia M.
过去十年在自闭症谱系障碍（ASD）风险基因的鉴定方面取得了很大成功，许多研究表明这些基因内存在功能丧失（LoF）突变。尽管如此，到目前为止，在自闭症治疗方法的开发方面尚未取得重大临床进展。鉴于LoF突变在自闭症病因中的作用，许多正在研发的治疗方法旨在在转录、翻译和蛋白质水平上挽救基因的单倍体不足效应。本综述将讨论从中心法则的各个层面开发的各种治疗技术，并举例说明：DNA层面的CRISPR激活（CRISPRa）和基因替换，mRNA层面的反义寡核苷酸（ASOs），以及蛋白质层面的小分子药物，随后综述这些治疗方法的当前给药途径。由于中枢神经系统（CNS）的穿透性对自闭症治疗至关重要，因此特别有必要评估在穿越血脑屏障（BBB）方面具有更高效率的给药方法。
The past decade has yielded much success in the identification of risk genes for Autism Spectrum Disorder (ASD), with many studies implicating loss-of-function (LoF) mutations within these genes. Despite this, no significant clinical advances have been made so far in the development of therapeutics for ASD. Given the role of LoF mutations in ASD etiology, many of the therapeutics in development are designed to rescue the haploinsufficient effect of genes at the transcriptional, translational, and protein levels. This review will discuss the various therapeutic techniques being developed from each level of the central dogma with examples including: CRISPR activation (CRISPRa) and gene replacement at the DNA level, antisense oligonucleotides (ASOs) at the mRNA level, and small-molecule drugs at the protein level, followed by a review of current delivery methods for these therapeutics. Since central nervous system (CNS) penetrance is of utmost importance for ASD therapeutics, it is especially necessary to evaluate delivery methods that have higher efficiency in crossing the blood-brain barrier (BBB).
登录
查看更多内容
影响因子：
48
作者：
Chavez A;Tuttle M;Pruitt BW;Ewen-Campen B;Chari R;Ter-Ovanesyan D;Haque SJ;Cecchi RJ;Kowal EJK;Buchthal J;Housden BE;Perrimon N;Collins JJ;Church G
通讯作者：
Church G
影响因子：
6.2
作者：
Benger M;Kinali M;Mazarakis ND
通讯作者：
Mazarakis ND
影响因子：
3.9
作者：
Blaxill, Mark;Rogers, Toby;Nevison, Cynthia
通讯作者：
Nevison, Cynthia
使用 TALEN 编辑的 MECP2 突变猴对 Rett 综合征进行建模。
影响因子：
64.5
作者：
Chen Y;Yu J;Niu Y;Qin D;Liu H;Li G;Hu Y;Wang J;Lu Y;Kang Y;Jiang Y;Wu K;Li S;Wei J;He J;Wang J;Liu X;Luo Y;Si C;Bai R;Zhang K;Liu J;Huang S;Chen Z;Wang S;Chen X;Bao X;Zhang Q;Li F;Geng R;Liang A;Shen D;Jiang T;Hu X;Ma Y;Ji W;Sun YE
通讯作者：
Sun YE
影响因子：
25
作者：
Chan KY;Jang MJ;Yoo BB;Greenbaum A;Ravi N;Wu WL;Sánchez-Guardado L;Lois C;Mazmanian SK;Deverman BE;Gradinaru V
通讯作者：
Gradinaru V