Genome engineering is extensively utilized in diverse scientific disciplines, advancing human welfare and addressing various challenges. Numerous genome engineering tools have been developed to modify genomic sequences. Among these, the CRISPR-Cas system has transformed the field and remains the most commonly employed genome-editing tool. However, the CRISPR-Cas system relies on induced double-strand breaks, with editing efficiency often limited by factors such as cell type and homologous recombination, impeding further progress. CRISPR-associated transposons (CASTs) represent programmable mobile genetic elements. CASTs identified as active were developed as CAST systems, which can perform RNA-guided DNA integration and are featured by high precision, programmability, and kilobase-level payload capacity. Moreover, CAST system allows for precise genome modifications independent of host DNA repair mechanisms, addressing the constraints of conventional CRISPR-Cas systems. It expands the genome engineering toolkit and is poised to become a representative of next-generation genome editing tools. This review thoroughly examines the research progress on CASTs, highlighting the current challenges faced in genome engineering based on CASTs, and offering insights into the ongoing development of this transformative technology.

中文翻译：

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拓展基因组工程的前沿：CRISPR 相关转座子的全面综述


基因组工程广泛用于不同的科学学科，促进人类福祉并应对各种挑战。已经开发了许多基因组工程工具来修饰基因组序列。其中，CRISPR-Cas 系统改变了该领域，并且仍然是最常用的基因组编辑工具。然而，CRISPR-Cas 系统依赖于诱导的双链断裂，编辑效率通常受到细胞类型和同源重组等因素的限制，阻碍了进一步的进展。CRISPR 相关转座子 （SET） 代表可编程的移动遗传元件。被鉴定为活性的 CART 被开发为 CAST 系统，该系统可以进行 RNA 引导的 DNA 整合，具有高精度、可编程性和千碱基级有效载荷能力等特点。此外，CAST 系统允许独立于宿主 DNA 修复机制进行精确的基因组修饰，解决了传统 CRISPR-Cas 系统的局限性。它扩展了基因组工程工具包，并有望成为下一代基因组编辑工具的代表。本文全面综述了 CASTs 的研究进展，强调了基于 CASTs 的基因组工程当前面临的挑战，并为这项变革性技术的持续发展提供了见解。