向大脑递送碱基编辑器的新观点

Emerging Perspectives on Prime Editor Delivery to the Brain.

作者信息

BenDavid Eli, Ramezanian Sina, Lu Yaoyao, Rousseau Joël, Schroeder Avi, Lavertu Marc, Tremblay Jacques P

机构信息

Laboratory of Biomaterials and Tissue Engineering, Department of Chemical Engineering, Institute of Biomedical Engineering, Polytechnique Montréal, Montréal, QC H3C 3A7, Canada.

Division of Human Genetics, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1V 4G2, Canada.

出版信息

Pharmaceuticals (Basel). 2024 Jun 11;17(6):763. doi: 10.3390/ph17060763.

DOI:10.3390/ph17060763

PMID:38931430

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11206523/

Abstract

Prime editing shows potential as a precision genome editing technology, as well as the potential to advance the development of next-generation nanomedicine for addressing neurological disorders. However, turning in prime editors (PEs), which are macromolecular complexes composed of CRISPR/Cas9 nickase fused with a reverse transcriptase and a prime editing guide RNA (pegRNA), to the brain remains a considerable challenge due to physiological obstacles, including the blood-brain barrier (BBB). This review article offers an up-to-date overview and perspective on the latest technologies and strategies for the precision delivery of PEs to the brain and passage through blood barriers. Furthermore, it delves into the scientific significance and possible therapeutic applications of prime editing in conditions related to neurological diseases. It is targeted at clinicians and clinical researchers working on advancing precision nanomedicine for neuropathologies.

摘要

碱基编辑作为一种精准的基因组编辑技术展现出了潜力，同时也有推动下一代纳米医学发展以解决神经疾病的潜力。然而，由于包括血脑屏障（BBB）在内的生理障碍，将碱基编辑器（PEs）——由与逆转录酶和碱基编辑引导RNA（pegRNA）融合的CRISPR/Cas9切口酶组成的大分子复合物——递送至大脑仍然是一项巨大的挑战。这篇综述文章提供了关于将PEs精准递送至大脑并穿过血屏障的最新技术和策略的最新概述及观点。此外，它还深入探讨了碱基编辑在与神经疾病相关病症中的科学意义及可能的治疗应用。它的目标读者是致力于推进神经病理学精准纳米医学的临床医生和临床研究人员。