Co-op Antisense Oligonucleotide Process Chemistry

This application is for a 6month student role from July December 2025. Resume review begins in January 2025.

The coop position provides an exciting opportunity to gain handson experience and exposure to the manufacturing process R&D activities. Working closely with the Antisense Oligonucleotide (ASO) chemistry and analytical development teams the coop will conduct the independent research project described below:  

Phenylacetyl disulfide (PADS) is a highly effective sulfurization reagent for the synthesis of antisense oligonucleotides when aged with a base for a minimum of 12 hours. However its utility is limited by a short shelf life of just 5 days which presents challenges for largescale manufacturing. Additionally aged PADS is ineffective for 5OH capping reactions. Conversely PADS solutions stored in an inert solvent designated as Fresh PADS demonstrate prolonged stability and are effective for 5OH capping. Nonetheless the use of Fresh PADS introduces a significant limitation: the sulfurization reactions proceed at a slow rate and require the addition of a strong base to accelerate the reaction and reduce side reactions. The employment of a strong base also risks the loss of cyanoethyl groups potentially compromising the stereoselectivity of subsequent coupling steps. 

The application of Fresh PADS in solidphase synthesis remains underexplored and its reaction conditions are not yet fully optimized. To address this it is essential to determine the optimal reaction parameters and evaluate their effects on the stereochemistry of the phosphate backbone and the impurity profile of the crude product. The proposed study involves solidphase synthesis experiments on a model antisense oligonucleotide aiming to identify the ideal concentration of PADS and activating base the appropriate solvent for the base the stoichiometry of PADS and base and the optimal reaction time. Each parameter will be optimized to achieve the best balance of sulfurization efficiency and impurity control. The optimized condition will be rigorously characterized and its impact on the stereochemistry of phosphorothioate centers relative to established processes will be assessed.  

Position Description

• Conduct experiments designed to gain insight into oligonucleotide synthesis processes.  
• Learn to program prepare and operate oligonucleotide synthesis equipment.  
• Prepare full length ASOs using solid phase synthesis techniques. Fully characterize and evaluate product purity by HPLCMS. 
• Document all experiments performed including analytical data collected and observations made. 
• Provide regular progress updates to supervisor on a daily or weekly basis. 
• Engage actively with supervisor to deepen understanding of principles experimental design and data interpretation. 
• Complete research report prior to the conclusion of the coop term. 

Qualifications :

• Excellent foundational knowledge of organic chemistry and electronic structure.   
• Advanced organic chemistry laboratory skills. Knowledge of proper procedures for handling volatile flammable and corrosive materials. 
• Experience with analytical HPLC/HPLCMS.  

To participate in the Biogen Internship Program students must meet the following eligibility criteria: 

• Legal authorization to work in the U.S. 
• At least 18 years of age prior to the scheduled start date 
• Be currently enrolled in an accredited community college college or university 

Education 

• Chemistry Ph.D. candidate or M.S. student. 

Additional Information :

Why Biogen

We are a global team with a commitment to excellence and a pioneering spirit. As a midsized biotechnology company we provide the stability and resources of a wellestablished business while fostering an environment where individual contributions make a significant impact. Our team encompasses some of the most talented and passionate achievers who have unparalleled opportunities for learning growth and expanding their skills. Above all we work together to deliver lifechanging medicines with every role playing a vital part in our mission. Caring Deeply. Achieving Excellence. Changing Lives.

At Biogen we are committed to building on our culture of inclusion and belonging that reflects the communities where we operate and the patients we serve. We know that diverse backgrounds cultures and perspectives make us a stronger and more innovative company and we are focused on building teams where every employee feels empowered and inspired. Read on to learn more about our DE&I efforts.

All qualified applicants will receive consideration for employment without regard to sex gender identity or expression sexual orientation marital status race color national origin ancestry ethnicity religion age veteran status disability genetic information or any other basis protected by federal state or local law. Biogen is an EVerify Employer in the United States.