Enhanced CRISPR technique amplifies its ability to suppress gene expression

In a groundbreaking development, researchers from Stanford University have created a CRISPR-Cas9 system that induces highly effective silencing of target genes for extended periods. This advancement, published in the journal BioDesign Research, could lead to better treatment options for various diseases, including cancer and genetic ailments.

The study, led by Dr. Lei S. Qi, a faculty fellow in Stanford ChEM-H and Assistant Professor in the Departments of Bioengineering and Chemical and Systems Biology at Stanford University, aims to develop a silencing system that prevents gene expression for a longer period, similar to a parking brake preventing wheel movement.

Dr. Qi, who has over 120 papers to his credit and more than 10 patents, is renowned for his work in CRISPR, Genome Editing, Synthetic Biology, and Cell Engineering. He received his Ph.D. degree in Bioengineering from UC Berkeley and UCSF (joint program), USA. He is also affiliated with Mammoth Biosciences, South San Francisco, United States.

The versatility of the CRISPR-Cas9 based gene editing is largely achieved by modifying the Cas9 protein itself. In this study, many effector proteins, including gene expression-altering enzymes, are fused with dCas9 for targeted binding to specific sites on the DNA. The endonuclease property of the Cas9 protein is removed, yielding a deactivated Cas9 (dCas9).

When fused with an activating or repressing transcription factor, the dCas9 complex upregulates or downregulates the target gene, respectively. In this case, the team achieved their goal by fusing dCas9 protein with a transcription repressor domain KRAB and DNA methylating domains of DNMT3L and DNMT3A. The construct, named dCas9-KAL, repressed gene expression for weeks in a cell-based reporter system.

The success in developing a robust and long-term epigenetic repressor has multifold implications. For instance, it could enable researchers to study gene functions over extended periods without the need for constant gene knockouts. Moreover, it offers a potential strategy for treating diseases caused by overactive genes, such as cancer.

The CRISPR-Cas9 system, originally discovered as a bacterial mode of defense against viruses, has become a popular research tool for gene editing. This latest development further expands its potential applications, underscoring the importance of ongoing research in this field.

For more details, you can access the research article at the following DOI: 10.34133/2021/9815820. The authors of the study belong to the group led by researchers at the University of California, Berkeley.

This research is a significant step forward in the ongoing quest to harness the power of CRISPR-Cas9 for therapeutic and research purposes. The potential applications of this technology are vast, and we can expect to see more groundbreaking discoveries in the near future.