Together, PAM machine learning algorithm (PAMmla) integrates machine learning and protein engineering to curate a catalogue of SpCas9 enzymes with distinct PAM requirements, motivating a shift away from generalist enzymes towards safe and efficient bespoke Cas9 variants.

Here, to enable scalable reprogramming of Cas9 enzymes, SCGE researchers combined high-throughput protein engineering with machine learning to derive bespoke editors that are more uniquely suited to specific targets.

Kiran Musunuru and Sonia Vallabh, panelists on "Concluding Panel: The Future of Targeted In Vivo Gene Editing" (3/3)

Rebecca Ahrens-Nicklas, "Personalized liver-directed corrective gene editing" (2/3)

Krishanu Saha, "Genome-wide CRISPR screening identifies cellular factors controlling nonviral genome editing efficiency" (Poster)

@sahakris.bsky.social (4/4)

Yong-hui Jiang, "Brain-wide genome editing via STEP-RNPs for treatment of Angelman syndrome" (3/4)

Kiran Musunuru, "LNP-mediated editing for treatment of cardiometabolic disease"
@kiranmusunuru.bsky.social (2/4)

Richard Lewis, PhD is the Principal Regulatory Device & Biologics Expert at Hyman, Phelps & McNamara, P.C.

More info about the SCGE Meet the Expert series can be found at scge.mcw.edu/meet-the-exp...

#RegulatoryGuidance #RareDisease #Preclinical #Biotech #BiomedicalResearch

James Valentine, JD, MHS is a Director at Hyman, Phelps & McNamara, P.C. where he assists medical product industry and patient advocacy organization clients in a wide range of regulatory matters relating to new drug and biologic development and approval.

With enhanced targeting versatility, Flex-Cas12a unlocks access to previously inaccessible genomic loci, providing new opportunities for both therapeutic and agricultural genome engineering. (3/3)

#Research #CRISPR #GeneEditing

To mitigate this constraint, SCGE researchers used a bacterial-based directed evolution assay combined with rational engineering to identify variants of Lachnospiraceae bacterium Cas12a with expanded PAM recognition. (2/3)

Our hope is that these documents can be useful to investigators that are developing gene editing therapies for rare diseases.

#Regulatory #GeneTherapy #RareDisease #BiotechResearch #BiomedicalResearch

The goal of the SCGE program is to accelerate the translation of genome editing therapies into the clinic. One of the ways we are working to achieve this goal is by publicly sharing successful strategies for starting clinical trials.