Engineer III, 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, including Vertex 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.

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.

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,…