Sr. Research Associate I, Drug Substance

Scribe Therapeutics is a molecular engineering company focused on creating best-in-class in vivo therapies that permanently treat the underlying cause of disease. Founded by CRISPR inventors and leading molecular engineers Benjamin Oakes, Brett Staahl, David Savage, and Jennifer Doudna, Scribe is overcoming the limitations of current genome editing technologies by developing custom engineered enzymes and delivery modalities as part of a proprietary, evergreen CRISPR by Design™ platform for CRISPR-based genetic medicine.

We are seeking a highly skilled Senior Research Associate with extensive expertise in nucleic acid chemistry to join the sgRNA Drug Substance team within the Process Science department. The primary goal of this role is to develop, optimize, and implement early-stage Chemistry, Manufacturing, and Controls (CMC) capabilities for our lead pre-clinical candidates. 

This position will involve close collaboration and study coordination with one or more R&D labs within the company as well as external collaborators and CDMOs, with a primary focus on advancing complex biologic therapies to human clinical studies and eventual licensure. As SRA – Oligonucleotide Chemistry, you will play a critical role as part of an expanding, cross-functional team to evaluate and apply emerging oligonucleotide chemistries and develop a deeper understanding of the interplay between sgRNA chemistry, RNP biochemistry and in vivo gene editing to unravel the underlying structure-function relationships between structurally complex sgRNA and RNPs. You will be required to develop additional competencies and apply practical skills and knowledge to solving a variety of applied scientific and technical problems. 

Qualified candidates should have a minimum of 8 years of extensive, hands-on laboratory experience, of which at least 2 years will be in the synthetic DNA/RNA industry. A basic understanding of conventional solid-phase oligonucleotide synthesis and downstream processing such as cleavage and deprotection, filtration/ lyophilization, purification and analytical characterization is highly desirable. Multiple years of experience with sample prep, buffer prep and the routine operation and general maintenance of various HPLC systems is essential. The ideal candidate will also possess a good understanding of the underlying principles of HPLC-based techniques such as IP-RP, IEX, HIC, HILIC, SEC and subsequent data analysis (e.g., Agilent, AKTA, Vanquish and associated software). Candidate must have 2 or more years of experience operating, troubleshooting, and maintaining various LC-MS instruments and should be experienced with gel-based analysis of DNA, RNA or its conjugates using techniques such as capillary electrophoresis and PAGE. Previous experience working with enzymes, performing enzyme-based assays, purification and characterization of protein or RNP (affinity chromatography, SEC, SDS-PAGE) is highly desirable.

Candidates should be self-starters, strategic thinkers, action-driven, thrive in a fast-paced environment, excel at managing multiple priorities, and be capable of providing decision-enabling data. 

 

Key Responsibilities:

• Support pre-clinical development of sgRNA and characterization assays to support CMC activities within the Drug Substance Process Sciences Team 
• Conduct experiments independently, document results using electronic lab notebooks, and prepare methods and SOPs 
• Analyze and present data at team and cross functional team meetings.
• Collaborate with CDMOs, CROs, and internal teams to coordinate development efforts and facilitate knowledge and tech transfer 
• Perform routine lab tasks such as buffer/solution preparation, inventory management and coordination of instrument maintenance

Required Skills and Background:

• Bachelor’s degree in chemistry or biochemistry with a minimum of 8 years of experience working in an industry lab. 
• Expertise in oligonucleotide synthesis, modification, and characterization techniques including routine and advanced analytical methods (e.g. UPLC/HPLC: IP-RP, AEX, SEC/SEC-MALS; LC/MS, NMR, CE, UV-Tm)
• Perform HPLC-based isolation, lyophilization, and buffer-exchange/TFF of oligonucleotides for analysis
• Experience with routine operation, general maintenance and interpretation of LC/MS analysis of oligonucleotides (ESI, Orbitrap, Q-TOF, MS/MS, etc) 
• Proficiency in techniques for enhancing process understanding, optimization and decision-making related to substance identification and chromatography
• Ability to write SOPs and train others in complex analytical assay execution 
• Familiarity with electronic lab notebooks like Benchling, Confluence
• Strong attention to detail and effective communication skills

Preferred Skills and Background:

• Hands-on experience with oligonucleotide synthesis on at least one platform (e.g., Mermade, Dr. Oligo, Oligopilot, etc), capable of handling air-sensitive and hazardous chemical reagents 
• Familiarity with regulatory and quality standards for oligonucleotide-based therapeutics, along with exposure to development processes supporting pre-clinical and clinical stages, is beneficial
• Knowledge of common chemical modifications of oligonucleotides and impurity analysis.
• Understanding of gene editing components including oligonucleotide guides, CRISPR endonucleases, and ribonucleoprotein (RNP) complexes, as well as experience in protein isolation, purification, and characterization is desired 
• Ability and willingness to learn and adapt to the requirements of a process-driven team.

Salary will be commensurate with experience. We will provide an intellectually stimulating, collegial and fast-paced environment. If you are ready to engineer the future of therapeutics, then we are excited to hear from you! Visit us at www.scribetx.com.  

We are committed to creating a diverse environment and are proud to be an equal opportunity employer. All qualified applicants will receive consideration for employment without regard to race, color, religion, gender, gender identity or expression, sexual orientation, national origin, disability, age, or veteran status.

At the time of posting, the base pay wage range for this role is $90,000-120,000 per year.  The offered pay range will depend on internal equity and the candidate’s relevant skills, experience, qualifications, training, and market data.  Additional incentives are provided as part of the complete package in addition to comprehensive medical and other benefits. 

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Last updated on Jul 18, 2024