Engineer 3 - mRNA Process Development-Downstream

Job Description:

Company Overview

Founded over a decade ago, CRISPR Therapeutics is a leading biopharmaceutical company focused on developing transformative gene-based medicines for serious human diseases. The Company has evolved from a pioneering research-stage organization into an industry leader, marking a historic milestone with the approval of CASGEVY® (exagamglogene autotemcel [exa-cel]), the world’s first CRISPR-based therapy, approved for eligible patients with sickle cell disease and transfusion-dependent beta thalassemia. CRISPR Therapeutics is advancing a broad and diversified pipeline across hemoglobinopathies, cardiovascular, autoimmune, oncology, regenerative medicine and rare diseases. The Company continues to expand its leadership in gene editing through the development of SyNTase™ editing, a novel and proprietary gene-editing platform designed to enable precise, efficient, and scalable gene correction. To accelerate and expand its impact, CRISPR Therapeutics has established strategic collaborations with leading biopharmaceutical partners, includingVertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug,Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco,California.

Position Summary

We are seeking an Engineer III to own downstream process development for mRNA drug substance and to carry those processes into GMP production at external CDMOs. This person will design, develop, and scale the purification process from bench through pilot scale in-house, then facilitate the technical transfer, engineering runs, and GMP campaign support at partner sites. The role is engineering-forward and externally facing.

Responsibilities

Downstream process development

• Develop and optimize downstream unit operations for mRNA drug substance: DNase treatment and reaction quench, clarification and depth filtration, chromatographic capture and polishing (oligo-dT affinity, ion exchange, reverse phase, hydrophobic interaction, core bead or multimodal), precipitation-based purification, TFF/UFDF, and sterile filtration
• Screen and select resins, membranes, filters, and single-use components; define binding capacity, loading, buffer, and elution conditions, and generate the data supporting each selection
• Develop impurity clearance strategies with defined logs or fold reduction for dsRNA, residual template DNA, protein and enzyme, residual nucleotides and small molecules, endotoxin, and truncated or aggregated RNA species
• Address mRNA-specific downstream challenges including viscosity at high concentration, shear sensitivity, aggregation and HMW species formation, membrane fouling, and product loss across the train

Scale-up and process fit to partner capability

• Assisting in building scale-up and scale-down models; define scaling parameters, sizing bases, and hold and hydraulic constraints for each unit operation
• Perform mass balance, yield accounting, and process fit analysis against each CDMO's actual equipment trains, single-use platforms, and facility constraints — and identify early where the process must be adapted or the site is not a fit
• Contribute to CDMO technical assessment and selection: capability gap analysis, equipment and automation compatibility, analytical readiness, and capacity
• Design the process to be transferable, favoring platform-standard equipment, commercially available consumables with second sources, and operating ranges that hold at a site you do not control

Technology transfer and external campaign execution

• Own downstream technology transfer to CDMOs end to end: transfer packages, process descriptions, scale-appropriate parameter tables, risk assessments, gap analyses, and resolution of site-specific questions
• Review and approve partner-generated documents — batch records, protocols, sampling plans, engineering run plans — and hold the line on parameters that matter while accommodating site practice where it does not
• Assist with technical readiness for engineering, toxicology, and GMP campaigns; run pre-campaign risk reviews and define the decision criteria and escalation path before the batch starts
• Serve as person-in-plant at partner sites: real-time data review, in-process decision support, and troubleshooting during execution
• Drive post-campaign activities: batch data review, yield and impurity reconciliation against the model, deviation investigations, CAPA input, and process improvements for the next campaign
• Support commercial and quality colleagues on technical content for statements of work, change controls, quality agreements, and tech transfer timelines

Cross-functional collaboration

• Partner with upstream and IVT process development to co-optimize the process rather than each half in isolation, particularly where reaction conditions drive downstream burden
• Work with Analytical Development on method suitability, sample plans, method transfer to the CDMO, and interpretation of purity and integrity data
• Interface with Formulation/LNP on drug substance attributes that affect drug product performance, and with Supply Chain on raw material and consumable lead times, second sourcing, and partner procurement timelines
• Present development and campaign data at program and platform forums

Minimum Qualifications

• BS in Chemical Engineering, Biochemical Engineering, Bioengineering, or related field with 4-6+ years of relevant industry experience; MS with 2-5+ years
• Hands-on downstream process development experience with biologics or nucleic acids, including chromatography and TFF at bench and pilot scale

• Demonstrated scale-up experience and a working command of mass balance, sizing, and engineering fundamentals applied to bioprocess unit operations
• Direct experience transferring a process to an external manufacturing partner, including authoring transfer documentation and supporting execution on site
• Experience with DoE and statistical analysis (JMP, Design-Expert, or equivalent)
• Strong written and verbal communication, and the ability to influence technical outcomes at a partner site without direct authority

Preferred Qualifications

• Direct mRNA, plasmid DNA, or oligonucleotide downstream experience, including oligo-dT affinity capture and dsRNA clearance
• Multiple completed GMP campaigns at CDMOs in a person-in-plant or technical lead capacity
• Experience with process characterization supporting late-phase development or BLA filing
• Familiarity with single-use technology selection, extractables and leachables considerations, and partner-site automation or recipe configuration
• Understanding of LNP formulation and drug product manufacturing as it constrains drug substance specifications

Competencies

• Collaborative – Openness, One Team
• Undaunted – Fearless, Can-do attitude
• Results Orientation – Delivering progress toward our mission. Sense of urgency in solving problems.
• Entrepreneurial Spirit – Proactive. Ownership mindset.

Due to the nature of their work, our manufacturing and lab-based positions are located fully on-site.  

Base pay range of $97,000 to $108,000+ bonus, equity and benefits

The range provided is CRISPR Therapeutics’ reasonable estimate of the base compensation for this role. The actual amount will be based on job-related and non-discriminatory factors such as experience, training, skills, and abilities.

CRISPR Therapeutics, Inc. is committed to equal employment opportunity and non-discrimination for all employees and qualified applicants without regard to a person's race, color, gender, age, religion, national origin, ancestry, disability, veteran status, genetic information, sexual orientation or any characteristic protected under applicable law.

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