Sanofi Group Post-Doctoral Fellow, Platform Innovation in La Jolla, California
Aptamers are promising as candidate therapeutics, but their composite natural nucleotides restrict their physicochemical properties. As a member of the Synthorx Platform Innovation team, the successful postdoctoral researcher will work towards using the Synthorx expanded genetic alphabet (unnatural base pair) to evolve aptamers and aptamer-drug conjugates with desired properties beyond those available with the four natural nucleotides. Efforts will include the exploration of aptamers conjugated to therapeutic proteins to modify receptor recognition or to target the proteins to specific cells or environments. The position to which the aptamers are conjugated will be controlled by expressing the protein in the Synthorx semi-synthetic organism. The semi-synthetic organism harbors the unnatural base pair in its DNA and transcribes it into RNA and then uses it to translate proteins with non-canonical amino acids that enable biorthogonal coupling. Efforts will also include evolving aptamers with unnatural nucleotides that are used to site-specifically conjugate moieties of interest such that they are included in the evolution process itself. The postdoctoral researcher will also aid in the coordination, planning, and execution of existing and new collaborations with other groups within Sanofi to deploy the technology. Publication of results will be a priority.
Use the Synthorx semi-synthetic organism to express proteins with non-canonical amino acids at different positions.
Optimize biorthogonal reactions to site-specifically couple aptamers to the proteins.
Collaboratively evaluate the effects of targeting the therapeutic protein using in vitro assays and mouse models.
Design and create libraries of DNA where the unnatural base pair is used to attach small molecules, including drugs or ligands that bind a therapeutically interesting target, and then subject the library to multiple rounds of SELEX to evolve the aptamer-drug conjugate for optimal activity (specificity and affinity).
Collaboratively evaluate the aptamer-drug conjugates using in vitro assays and mouse models.
PhD in appropriate field.
Experience with SELEX (aptamer evolution).
Experience with protein expression and/or biorthogonal chemistry beneficial.
Ability to work both independently and within a team.
Must have permanent US work authorization
Sanofi Inc. and its U.S. affiliates are Equal Opportunity and Affirmative Action employers committed to a culturally diverse workforce. All qualified applicants will receive consideration for employment without regard to race; color; creed; religion; national origin; age; ancestry; nationality; marital, domestic partnership or civil union status; sex, gender, gender identity or expression; affectional or sexual orientation; disability; veteran or military status or liability for military status; domestic violence victim status; atypical cellular or blood trait; genetic information (including the refusal to submit to genetic testing) or any other characteristic protected by law.
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