Cell Biology Lead - CRISPR Cures Technology Core

Cell Biology Lead - CRISPR Cures Technology Core (9611C) 86277 Position Summary

Reporting to the Director of the Biohub-IGI Center for Pediatric CRISPR Cures, the SRA3 performs experimental work aimed at advancing to first-in-human clinical trials CRISPR-based approaches to treat inborn errors of immunity. Working in close partnership with, and supporting, the effort of physician-scientists leading the nonclinical efforts in the Beacon, the SRA3 is responsible for the design, prosecution, and analysis of experiments assessing the potency, specificity, and biological activity of candidate therapeutic gene editor compositions.

The Innovative Genomics Institute has established a Center for Pediatric CRISPR Cures. Its goal is to develop and advance to the clinic gene-editing-based therapies for two severe inborn errors of the immune system. The SRA3 represents a linchpin position within the nonclinical (IND-enabling) component of the effort in both leading on, and executing, on a range of experiments to establish the efficacy and safety of therapeutic candidate gene editors, and, when scientifically relevant, the design, development, and optimization of assays to assess efficacy/safety.

• Perform experiments in primary and transformed human cells to assess gene editor efficacy. Experimentally identify on a cell-type-by-cell-type basis optimal cell husbandry conditions for gene editing experiments. Optimize tissue culture conditions for maximal viability post-gene editor transfer. Develop and perform cell phenotyping assays to evaluate physiological consequences of gene editing. Isolate cellular material (protein, RNA, DNA) for downstream analytics optimizing for yield and sample integrity.
• Perform experiments in primary and transformed human cells to assess gene editor safety. Optimize cell husbandry conditions for dose-response-curve experiments in primary and transformed human cells. Develop and deploy cell phenotyping assays to assess on-target engagement following gene editor delivery. Isolate nucleic acids (DNA and RNA) from gene-edited cell preparations. Prepare nucleic acid libraries for off-target assessment. Optimize and deploy computational procedures to determine genome/transcriptome-wide consequences of gene editing.
• Assess gene editing outcomes using established cell- and nucleic-acid-based analytical pipelines. Following introduction of gene editors into primary and transformed human cells, use cell sorting and, where appropriate, microscopy-based procedures to characterize the cells at the phenotypic level. Extract nucleic acids from gene-edited cells and assess gene editing efficiency using NGS, ddPCR, and RT-qPCR methods.
• Design, develop, and prosecute novel analytical procedures to assess gene editing outcomes. Identify project-critical analytical endpoints required to address Agency feedback. Working closely with project nonclinical leads and analytical core lead, identify suite of assays to be developed to measure these endpoints. Iterate on a design-build-test process to reduce the assays to operational practice.
• Supervise junior personnel in prosecution of efficacy/safety/analytical studies. On an as-need basis, provide operational guidance on wet-lab and analytical procedures to SRA1/2 team members across all nonclinical functionalities to ensure adherence to project timelines and milestones.
• Prepare and present summaries of experiments performed and resulting data at project team meetings.
• Act as the lead technical writer on study reports for regulatory submissions to the FDA CBER.

• Extensive hands‑on experience with mammalian tissue culture, including primary/stem cells.
• Extensive hands‑on experience with nucleic-acid-based assays in gene editing space (qPCR, NGS, ddPCR).
• Robust experience with cell phenotyping assays in gene editing space (FACS, microscopy).
• Extensive experience with visualization, analysis, and presentation of results in gene editing space.
• Bachelor of Science in Biology, MCB, BioE, and/or equivalent experience/training.

• Direct experience working in a cross-functional team setting developing a…