On Nov 18th, research team from Aarhus University published a groundbreaking research paper titled "Orthogonal transcriptional modulation and gene editing using multiple CRISPR/Cas systems" in the journal "Molecular Therapy" (impact factor: 12.4).
This study investigates CRISPR/Cas-based transcriptional activation (CRISPRa) and interference (CRISPRi) for gene regulation by recruiting or fusing transcriptional regulators to a nuclease-deficient Cas (dCas) protein. The researchers explore RNA delivery and transcriptional engineering by evaluating combinations of RNA-delivered dCas and transcriptional modulators. They use dCas9 from Staphylococcus aureus and Streptococcus pyogenes to modulate gene expression, upregulating some genes while downregulating others.
Additionally, the study establishes trimodal genetic engineering by combining orthogonal transcriptional regulation with gene knockout using Cas12a ribonucleoprotein (RNP). To simplify this process, they optimize parameters for implementing truncated sgRNAs, balancing the ratio of Cas9 protein to sgRNA to avoid cross-complexation and maintain knockout and activation efficiencies.
High efficiencies of this trimodal genetic engineering are demonstrated in primary human T cells, preserving their basic health and functionality. This research highlights the versatility and potential of complex genetic engineering using multiple CRISPR/Cas systems, suggesting applications in regenerative medicine and therapies for more advanced treatments.
In conjunction with the research study, sgRNAs were synthesized by SBS Genetech. Since 2000, SBS Genetech has been at the forefront of providing solutions in life sciences. We offer safer, superior quality, and more cost-effective products to preeminent researchers in more than 60 countries, empowering them to make new discoveries in biology. Our products have been widely utilized in academic research, with results often published in leading academic journals like Science, Cell, Cancer Cell, and Cell Metabolism. We firmly believe that through continuous innovation and research, we will continually infuse new vitality and possibilities into the field of life sciences.