Profluent Scientist II - Sr. Scientist to build and apply experimental workflows characterizing CRISPR base editor specificity and safety. Lead off-target assessments and collaborate cross-functionally.
Responsibilities
Build and lead Profluent’s strategy for base editor specificity assessment, with an emphasis on base-editor-relevant off-target discovery and validation workflows such as CHANGE-Seq-BE and related biochemical, cell-based, and targeted sequencing approaches
Develop, optimize, benchmark, and apply orthogonal methods to evaluate editing specificity, including workflows for base editors, nucleases, and broader genomic integrity assessment across relevant experimental systems
Design and execute studies to identify, prioritize, and validate potential off-target editing events, integrating assay development, NGS library preparation, sequencing QC, and data interpretation in partnership with computational biology and program teams
Generate high-quality, decision-enabling datasets that inform editor engineering, guide/editor selection, delivery conditions, candidate nomination, and program development strategy
Collaborate cross-functionally with protein engineering, cell biology, gene editing, bioinformatics, automation, and program teams to integrate specificity workflows into Profluent’s broader R&D infrastructure
Establish robust experimental processes, documentation, and analysis frameworks to support reproducibility, scalability, assay qualification, and potential regulatory-facing genomic safety packages
Present results and clearly communicate experimental strategy, timelines, risks, milestones, and program implications to diverse scientific and company stakeholders
Provide mentorship and guidance to junior team members and peers, helping align goals, troubleshoot experiments, and maintain high standards for execution and interpretation
Stay current with emerging technologies in CRISPR specificity, base editing, off-target discovery, targeted validation, genomic integrity assessment, and therapeutic genome editing
Qualification
Hands-on experience developing
Required
PhD (or equivalent) in molecular biology, genomics, genome editing, biochemistry, bioengineering, genetics, chemical biology, or a related field with 2-4 years of relevant industry experience in genome editing specificity and genomic safety assessment
Deep expertise and hands-on experience with CRISPR-based genome editing systems, particularly base editors, and a strong understanding of modality-specific specificity risks such as DNA off-target editing, RNA off-target editing, bystander editing, indels, and unintended editing outcomes
Hands-on experience developing, optimizing, or applying NGS-based workflows for genome editing analysis, such as CHANGE-seq, CHANGE-seq-BE, GUIDE-seq, SITE-seq, CIRCLE-seq, Digenome-seq, DISCOVER-seq, INDUCE-seq, targeted amplicon sequencing, rhAmpSeq/AmpSeq-like workflows, hybrid capture, RNA-seq, WGS, or related approaches
Strong experimental background in molecular biology, mammalian cell culture, genome editing reagent delivery, NGS library preparation, assay troubleshooting, and quantitative analysis of editing outcomes
Experience interpreting complex sequencing datasets and collaborating with bioinformatics or computational biology teams to analyze off-target discovery, targeted validation, variant calling, RNA editing, indel profiles, or genomic integrity data
Ability to design rigorous experiments with appropriate controls, replicates, sensitivity considerations, and clear decision criteria
Experience with high-throughput or semi-automated workflows, process development, assay qualification, data tracking, and reproducible execution in a fast-paced research environment
High level of attention to detail and commitment to generating high-quality, decision-enabling data
Experience with cross-functional collaboration in a biotechnology setting, particularly with protein engineering, cell biology, computational biology, translational, or program teams
Excellent communication skills and ability to present complex scientific concepts, datasets, limitations, and recommendations to colleagues and stakeholders
Strong track record of managing complex projects, mentoring junior scientists, and driving workstreams from exploratory development through implementation
Experience with therapeutic genome editing programs and genomic safety packages for candidate nomination, IND-enabling studies, or regulatory-facing documentation
