Translating Genome Editing of Stem Cells to the Clinic with Improved Cas9 Specificity
In conjunction with The CRISPR Journal, Aldevron offered this instructive webinar on the CRISPR/Cas9 system. A powerful genome-editing tool that can selectively modify and correct an abnormal DNA sequence inside living cells with single-nucleotide precision, CRISPR is being used to develop groundbreaking treatments for patients without curative therapies.
|Matthew Porteus, MD, Ph.D.
Associate Professor, Department of Pediatrics and Institute of Stem Cell Biology and Regenerative Medicine; Stanford University
- Run time - 1:01:20
- Introduction - 00:01
- Matthew Porteus - 01:42
- Tom Foti - 31:51
- QA - 41:00
Presentation summaryThe drive to maximize safety of genome editing using this system can call for improved versions of CRISPR/Cas9 and related nucleases that maintain on-target activity, an essential feature for any genome editing approach, while decreasing potentially harmful, off-target nuclease activity.
Although there have been several publications describing engineered Cas9 proteins with diminished off-target effects, we found these examples were also significantly lower in on-target activity, probably due to over-engineering, to the extent that their use for clinical application would be limited.
Integrated DNA Technologies (IDT) is the patent holder for this high-fidelity CRISPR-associated nuclease that will be described in the presentation. The IDT authors, in collaboration with Matthew Porteus, recently published their data in the August edition of Nature Medicine. The paper reports that this new high-fidelity version of Cas9 maintains on-target activity and decreases off-target activity by >10-fold in clinically relevant cell types using clinically relevant RNP delivery methods.
This new high-fidelity Cas9 variant and how it is being used to develop novel human cell therapeutics is described in this webinar. In addition to the technical details presented, Foti discussed availability and product details of the research grade and GMP high-fidelity version of Cas9 which is marketed under Aldevron’s trade name, SpyFiTM Cas9 Nuclease.