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DTSTART:20260329T030000
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DTSTAMP:20260415T001856Z
UID:698aeafda7e08601921534@ist.ac.at
DTSTART:20260401T150000
DTEND:20260401T163000
DESCRIPTION:Speaker: David Taylor\nhosted by Prof. Jack Bravo\nAbstract: CR
 ISPRCas9s clinical utility is constrained by strict PAM requirements and t
 he inability to package large nucleases into AAV vectors. We engineered a 
 modular Cas9\, split into a nuclease scaffold and an exchangeable PAM-inte
 racting domain (PID). This architecture enables one scaffold to function w
 ith multiple PIDs\, allowing ultra-multiplexing and simple PID swapping to
  target all disease-relevant loci. Guided by cryo-EM\, we identified funct
 ional split sites\, validated activity with a GFP reporter assay\, and res
 tored fast cleavage kinetics using intein-mediated ligation. Exchanging PI
 Ds broadened PAM compatibility significantly\, with several split chimeras
  achieving robust editing across any site in human cells. This precision n
 uclease system offers a compact\, PAM-flexible platform that fits within a
  single AAV and establishes a path toward versatile\, clinical genome-edit
 ing therapies.
LOCATION:Central Bldg / O1 / Mondi 2a (I01.O1.008)\, ISTA
ORGANIZER:jbravo@ist.ac.at
SUMMARY:David Taylor: &quot\;Reengineering CRISPR-Cas effectors&quot\;
URL:https://talks-calendar.ista.ac.at/events/6321
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