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Amritava (Tava) Das, Saha Lab, “In Vitro and In Silico Modeling of Efficacious Somatic Cell Genome Editing Strategies for Recessive and Polygenic Diseases”
February 23 @ 12:00 pm - 1:00 pm
The UW Stem Cell & Regenerative Medicine Center will continue to offer its weekly seminar online in a live (synchronously) format, so that you, as all can continue to participate in the Q & A session in real time.
To connect and join our live Tuesday Stem Cell Seminar Series (now online), please click on this public link (be sure to allow mic / video access when prompted in browser): https://us.bbcollab.com/guest/872ec396918e4a2c825824e04f21bd01
We do encourage you all to review the instructions, linked below, in order to orient yourselves to this online platform environment. You are also welcome to jump into the room and test your ability to connect, including turning on your audio and video, prior to the scheduled event time. Our center’s Administrator, Hollie, will be in the room starting at 11:00 AM CT the day of and can offer assistance as time allows.
If you have any questions, please contact Hollie: firstname.lastname@example.org
**STUDENTS: If you are a current student, please join the course room via the BBCollaborate option in your Canvas course portal.
In Vitro and In Silico Modeling of Efficacious Somatic Cell Genome Editing Strategies for Recessive and Polygenic Diseases
Amritava (Tava) Das
Morgridge Institutes for Research,
Wisconsin Institutes for Discovery
Compound heterozygous recessive or polygenic diseases could be addressed through gene correction of multiple alleles. However, targeting of multiple alleles using genome editors could lead to mixed genotypes and adverse events that amplify during tissue morphogenesis. Here we demonstrate that Cas9-ribonucleoprotein-based genome editors can correct two distinct mutant alleles within a single human cell precisely. Gene-corrected cells in an induced pluripotent stem cell model of Pompe disease expressed the corrected transcript from both corrected alleles, leading to enzymatic cross-correction of diseased cells. Using a quantitative in silico model for the in vivo delivery of genome editors into the developing human infant liver, we identify progenitor targeting, delivery efficiencies, and suppression of imprecise editing outcomes at the on-target site as key design parameters that control the efficacy of various therapeutic strategies. This work establishes that precise gene editing to correct multiple distinct gene variants could be highly efficacious if designed appropriately.