Scientist II - Sr. Scientist, CRISPR Specificity & Genomic Safety

Profluent is an AI-first protein design company. Founded in 2022, we develop deep generative models to design and validate novel, functional proteins to revolutionize biomedicine. Based in Emeryville, CA, we are backed by leading investors including Altimeter Capital, Bezos Expeditions, Spark Capital, Insight Partners, Air Street Capital, AIX Ventures, and Convergent Ventures, and have raised over $150M to date. Profluent is seeking a creative and enthusiastic Scientist II - Sr. Scientist to build and apply experimental workflows that characterize the specificity, safety, and developability of our personalized CRISPR base editing platform. This role will initially focus on establishing and scaling base-editor specificity workflows, including biochemical and cell-based approaches such as CHANGE-seq-BE and related methods for identifying DNA and RNA off-target activity. In the longer term, the candidate will spearhead off-target assessments for novel gene editing platforms such as engineered recombinases. The candidate will work closely with protein engineering, cell biology, bioinformatics, automation, and program teams to generate decision-quality datasets that guide editor design, candidate selection, and therapeutic program development. This person will be responsible for benchmarking assays, interpreting NGS-based specificity data, identifying limitations and opportunities across methods, and building robust workflows that can be deployed across editing modalities and disease-relevant contexts. This is an excellent opportunity to shape how AI-designed genome editing systems are evaluated and advanced, and to work cross-functionally with a diverse team of experts across machine learning, protein engineering, cell biology, genomics, and gene editing. 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 Qualifications 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 Preferences Experience with therapeutic genome editing programs and genomic safety packages for candidate nomination, IND-enabling studies, or regulatory-facing documentation Experience working with disease-relevant primary cells, ex vivo edited cells, iPSC-derived systems, or other therapeutically relevant model systems Familiarity with ML-guided enzyme engineering campaigns and how specificity datasets can inform editor design, model evaluation, and candidate prioritization Expertise in protein purification of genome editors for use in biochemical off-target assays What We Offer High-growth opportunity with meaningful impact on the future of protein design Competitive compensation package with equity participation 401(k) with a strong employer match Comprehensive benefits including health/dental/vision insurance Generous PTO policy and commitment to work-life balance Professional development opportunities in a cutting-edge field at the intersection of AI and biology Profluent Bio, Inc is an equal opportunity employer promoting diversity and inclusion in the workspace. We do not discriminate on the basis of race, color, religion, marital status, age, national origin, ancestry, physical or mental disability, medical conditions, veteran status, sexual orientation, gender (including gender identity and gender expression), sex (which includes pregnancy, childbirth, and breastfeeding), genetic information, taking or requesting statutorily protected leave, or any other basis protected by law. Work Authorization Requirement Applicants must have ongoing work authorization in the United States that does not require employer sponsorship. Sponsorship will not be provided now or at any time in the future for this position. Employment Eligibility Verification Legal authorization to work in the United States is required. In compliance with federal law, all persons hired must verify their identity and work eligibility and complete the required employment verification form upon hire. Hiring Salary Range

$147,000—$177,000 USD