The CRISPR-Cas system has not only revolutionized the field of genome

engineering, but also reinforced gene therapy development. Since the first

gene editing application in mammalian cells, several generations of

CRISPR-Cas tools have been developed and have exhibited tremendous

therapeutic potentials. The classical CRISPR-Cas realizes genome editing

by generating double strand DNA break (DSB). Recently, two advanced

CRISPR technologies - base editing and prime editing - were developed to

expand the genome editing toolbox. These two are able to generate precise

and versatile genome editing without relying on DSB, all of which are

beneficial in particular to gene therapy application. The aim of this collection

is to review the development of CRISPR technologies and discuss their

potentials/issues as therapeutics.