Enhanced CRISPR technique amplifies its suppressive ability
In a groundbreaking development, a team of scientists led by Dr. Lei S. Qi at Stanford University has created a CRISPR-Cas9 system capable of inducing highly effective silencing of target genes for extended periods. The research, which was published in the journal BioDesign Research, has the potential to revolutionise treatment options for various genetic ailments, including cancer.
Dr. Qi, an Assistant Professor at the Department of Bioengineering, Department of Chemical and Systems Biology, and a faculty fellow in Stanford ChEM-H, is a major contributor to the development of CRISPR technology for genome engineering. His research interests include CRISPR, Genome Editing, Synthetic Biology, and Cell Engineering.
The success in developing a robust and long-term epigenetic repressor, named dCas9-KAL, was achieved by fusing the dCas9 protein with a transcription repressor domain KRAB (Krüppel-associated box) and DNA methylating domains of DNMT3L and DNMT3A- two potent epigenetic modifiers.
In their research, the scientists tested the silencing capacity of the dCas9-KAL construct in a cell-based reporter system. When stably integrated into human cells expressing fluorescent protein EGFP, the dCas9-KAL construct repressed fluorescence for weeks, demonstrating its effectiveness and longevity.
While the gene-altering ability of such complexes is transient, as the effects persist only while the effector domains of the regulatory proteins remain physically bound or actively targeted to the region of interest, the versatility of CRISPR-Cas9 based gene editing is largely achieved by modifying the Cas9 protein itself. Many effector proteins, including a wide variety of gene expression-altering enzymes, are then fused with dCas9 for targeted binding to specific sites on the DNA. When fused with an activating or repressing transcription factor, the dCas9 complex upregulates or downregulates the target gene, respectively.
The DOI for the research is 10.34133/2021/9815820. At the time of the research, Dr. Qi was affiliated with Stanford University, but currently, he is affiliated with Mammoth Biosciences, South San Francisco, United States. Dr. Qi received his Ph.D. degree in Bioengineering from UC Berkeley and UCSF (joint program), USA.
The implications of this research are vast, particularly in the field of medicine. The long-term silencing of specific genes could lead to better treatment options for cancer and other genetic ailments, where the overexpression or underexpression of certain genes is a significant contributing factor.
However, it is important to note that the names of the authors for the paper titled "Durable CRISPR-based epigenetic silencing" published in the journal BioDesign Research could not be determined from the search results.
Dr. Qi has more than 120 papers, more than 10 patents, and several renowned awards to his credit. His ongoing work continues to push the boundaries of CRISPR technology and its potential applications.
