The Progress of Prime Editing in The Treatment of Neurogenetic Diseases

Xuannan Zhuang

doi:10.54097/mjbm4647

Authors

Xuannan Zhuang

DOI:

https://doi.org/10.54097/mjbm4647

Keywords:

prime editing: Gene editing, neurogenetic diseases, AHC.

Abstract

Due to the non-renewable nature of central nervous system cells, genetic heterogeneity and the mechanism of dominant negative mutations, neurogenetic diseases have long lacked effective radical treatment methods. Traditional gene editing techniques such as CRISPR-Cas9 rely on DNA double-strand breaks (DSB), which are inefficient and pose safety risks in non-dividing neurons. Prime Editing (PE), as a disruptive "search - replace" type of precise gene editing technology, realizes all 12 base conversions, small fragment insertions and deletions without introducing DSB, bringing unprecedented opportunities for the treatment of neurogenetic diseases. This article will elaborate on the technical principles of PE and its unique advantages in the treatment of neurogenetic diseases by combining experimental research and literature reports in recent years. It will focus on summarizing the latest breakthrough progress of PE in the preclinical research of alternating hemiplegia (AHC) in children, especially its symptom reversal and functional recovery ability demonstrated in in vivo treatment. Meanwhile, this article delves deeply into the core challenges faced by the clinical transformation of PE, such as in vivo delivery efficiency and interference with mismatch repair (MMR) systems, and looks forward to the future directions of addressing these challenges through carrier engineering innovation. PE technology is expected to drive the transformation of neurogenetic diseases from symptomatic treatment to one-time radical cure in a new era.

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