Circulation:“垃圾基因”并不是一无是处,它可以治疗心脏病
2017/08/29
加州大学洛杉矶分校和霍华德休斯医学研究所的科学家近日发现,LeXis这个“垃圾DNA”,或许并不是一无是处,或许可以使用它来治疗心脏病。研究成果发表在《Circulation》杂志上。


加州大学洛杉矶分校和霍华德休斯医学研究所的科学家成功地使用了一种抑制胆固醇水平的基因作为一种治疗方法,目的是减少家族性高胆固醇血症引起的血小板增多。在临床预实验中,研究人员发现LeXis基因可降低胆固醇和减少动脉阻塞,而且这种治疗方法似乎还可以减少肝细胞中的脂肪堆积。该研究发表在《Circulation》杂志上。

家族性高胆固醇血症(FH)是一种遗传病,又称家族性高β脂蛋白血症。临床特点是高胆固醇血症、特征性黄色瘤、早发心血管疾病家族史。

LeXis基因属于一组独特的基因,一直被认为是“垃圾DNA”,因为科学家认为它们没有什么作用。然而,人类基因组计划的证据表明,LeXis等基因实际上是活跃的。这些基因被称为长链非编码RNA(lncRNAs),是生物学的研究热点之一。

研究人员想测试单次注射基因LeXis是否能减缓心脏病的发展。为此,他们给小鼠注射了“LeXis”,并设置对照组,然后给小鼠喂食了15周的高盐高胆固醇的食物——相当于快餐汉堡和炸薯条。随后研究人员测量了心脏病的进展。

尽管之前的研究已经表明IncRNAs很重要,但这是首次表明IncRNAs可以被用于基因治疗来治疗人类疾病。“垃圾基因”未来可能有助于治疗家族性高胆固醇血症和其他难以治疗的疾病。

本文作者是加州大学洛杉矶分校的Xiaohui Wu,Zhengyi Zhang ,Tamer Sallam博士,霍华德休斯医学研究所的Peter Tontonoz博士,Marius Jones博士和David Salisbury博士。

他们下一步将在大型动物身上确认这一发现,并结合目前可用的治疗方法来测试这一疗法。

参考资料

Gene therapy using ‘junk DNA’ could lower risk for heart disease

所有文章仅代表作者观点,不代表本站立场。如若转载请联系原作者。
查看更多
  • Long Noncoding RNA Facilitated Gene Therapy Reduces Atherosclerosis in a Murine Model of Familial Hypercholesterolemia

    Familial hypercholesterolemia (FH) is an autosomal-dominant disorder characterized by severe elevations in low-density lipoprotein cholesterol (LDL-C) levels and a 20-fold increased risk of premature cardiovascular disease. Although multiple causative genes have been identified, most FH cases are because of mutations in the LDLR, proprotein convertase subtilisin/kexin type 9, or apolipoprotein B genes.1 Recent studies suggest that many patients with FH fail to achieve optimal LDL-C reduction despite high-intensity statin use and the recent addition of proprotein convertase subtilisin/kexin type 9 inhibitors.1 Adeno-associated virus (AAV)-based gene therapy is currently approved or in clinical trials for >80 human diseases, and to address the substantial gap in treatment for patients with severe FH, hepatic AAV-LDL receptor-based gene therapy is currently in phase II clinical trials. Long noncoding (lnc) RNAs form the vast majority of transcriptionally active regions and are arbitrary defined as transcripts >200 bps that biochemically resemble mRNA and yet do not template protein.2 Although multiple lines of evidence implicate lncRNAs in a range of developmental processes and diseases, few lncRNA knockout studies have yielded robust phenotypes or demonstrated that proposed mechanisms are operational in vivo. Furthermore, lncRNA regulatory circuits have not been well explored for their potential therapeutic utility. We recently showed that the lncRNA liver-expressed liver X receptor-induced sequence (LeXis) orchestrates cross-talk between the liver X receptor and sterol regulatory element-binding protein transcription factors to maintain hepatic sterol content …

    展开 收起
发表评论 我在frontend\modules\comment\widgets\views\文件夹下面 test