Gene therapy experts TJ Cradick and Andrew Kernytsky discuss the issues surrounding unintended off-target editing of genetic tools like CRISPR

For this high-tech emerging field within biotech, it is important to get safety right. They discuss the keys to understanding the possible range of edits, choosing the right assay, assessing and reporting the possible outcomes, and more.

The Experts

TJ Cradick, PhD is a CRISPR and gene editing expert with over 22 years of experience in cell and gene therapy research and management. In 2015, he joined CRISPR Therapeutics as the second employee and Head of Genome Editing. Subsequently, he served as the Chief Scientific Officer (CSO) at Excision BioTherapeutics, expanding his expertise in IND, regulatory affairs, intellectual property, and clinical trials.

Educated at MIT and UCSF,  Dr. Cradick joined Sangamo Biosciences in 2000, designing Zinc Finger proteins and Zinc Finger Nucleases (ZFNs). At the University of Iowa, he developed the first nucleases that specifically cleaved Hepatitis B virus DNA, created bioinformatics tools, and published the Surveyor gene editing assay. As a faculty member at Georgia Tech and Emory, he conducted pioneering research on ZFNs, TAL effector nucleases (TALENs), and CRISPR, co-authoring highly cited publications and developed bioinformatic and machine learning tools such as PROGNOS, SAPTA, and COSMID. Additionally, the group initiated the hemoglobinopathies experiments with CRISPR Therapeutics that led to the development of Casgevy. Dr. Cradick's extensive experience also includes developing assays and computational methods for IND submissions and clinical trials. For more information and access to his talks, papers, and consulting projects, please visit GeneEditingFrontiers.com.

Andrew Kernytsky began working in the CRISPR/Cas9 field in 2015 by building the on- and off-target editing assessment platform at CRISPR Therapeutics. This was instrumental in getting the Sickle Cell Disease therapy, Casgevy, across the finish line as the first CRISPR gene editing product approved by the FDA.

While this got him hooked on using gene editing for making medicines, he earlier started in science by earning a Ph.D. in computational biology from Columbia University. That work in Burkhard Rost’s lab used machine learning (or AI as it is now often called) to predict protein function from amino acid sequences using neural networks and genetic algorithms. He then switched from studying proteins to genes by joining the team at the Broad Institute that was building algorithms for the Genome Analysis ToolKit (GATK), a package that is now widely used for analyzing next generation sequencing (NGS) data. Working with NGS then led him to Agios Pharmaceuticals where he analyzed the large volumes of cancer sequencing data being generated by The Cancer Genome Atlas (TCGA) consortium to find new cancer metabolism therapeutic targets. Also there, he found that often the best computational biology is that done with lab scientists. And so, working with the lab teams, he used genome wide methylation experiments combined with pathway bioinformatics to elucidate the epigenetic mechanism of action of Agios’ lead cancer metabolism drug that is now approved for treatment of cancers with isocitrate dehydrogenase (IDH) mutations.

Andrew now works with organizations (companies and venture capital firms) to build gene editing programs by providing consulting on: gene editing, computational biology, regulatory writing / strategy / review, new venture evaluation / creation, and most critically –dealing with clinical holds and avoiding them in the first place.

And here’s a fun bit: the love of acronyms using the four DNA nucleotides (like TCGA) led to his favorite group name when at CRISPR Therapeutics: the Genomics And Computational biology Team (GACT).