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Sanofi Group Scientist I – Platform Innovation in San Diego, California

Responsibilities

Synthorx/Sanofi is seeking a eukaryotic cell/strain engineer to lead the development of a semi-synthetic eukaryotic organism to be used for the development of next generation protein therapeutics. This work will extend a platform based on the already successfully developed semi-synthetic prokaryotic organism (based on E. coli) that is currently being used to produce novel therapeutic protein candidates. Briefly, the prokaryotic semi-synthetic organism is based on the use of an unnatural base pair formed between two synthetic nucleotides and the cell engineering to facilitate the import of the requisite unnatural nucleoside triphosphates provided in the growth media. Once imported, the prokaryotic cell uses the triphosphates to replicate DNA and then transcribe genes that include the unnatural nucleotides into mRNA and tRNA with cognate unnatural codon/anticodon pairs, which are used at the ribosome to translate proteins containing non-canonical amino acids that facilitate their development as therapeutics.

As efficient translation with the unnatural codon/anticodon pairs has already been demonstrated in CHO and HEK cells (A. X.-Z. Zhou, K. Sheng, A. W. Feldman, F. E. Romesberg (2019) Progress toward eukaryotic semisynthetic organisms: Translation of unnatural codons. J Am Chem Soc 141:20166–20170), we are now seeking a scientist to lead the effort toward the creation of semi-synthetic eukaryotic organisms by engineering them to import the triphosphates and then use them for replication and transcription.

In addition, the successful candidate will lead the effort to use the semi-synthetic organism to produce proteins containing non-canonical amino acids for development as next generation therapeutics. The successful candidate will also aid in the coordination, planning, and execution of existing and new collaborations with other groups within Sanofi to explore the development of novel therapeutics for different applications.

Key Responsibilities

• Explore the expression of different nucleotide transporters in eukaryotic cells (e.g. yeasts (S. cerevisiae, P. pastoris) or human cell lines (CHO, HEK).

• Perform cell uptake assays with the unnatural nucleoside triphosphates as well as with modified variants designed to facilitate uptake.

• Collaboratively design and implement experiments to characterize and/or optimize the retention of the unnatural base pair during DNA replication and transcription.

• Characterize the fidelity with which non-canonical amino acids are incorporated in expressed proteins.

• Support efforts to optimize the production of proteins with non-canonical amino acids, including one or multiple instances of the same or two different non-canonical amino acids.

• Oversee collaboration with other groups within Sanofi for the broad use of the developed semi-synthetic organism.

• Collaborate with other groups within Sanofi to produce next-generation protein therapeutics.

Basic Qualifications

• PhD in appropriate field. No postdoctoral experience required.

• Experience with eukaryotic genetics (e.g. yeasts (S. cerevisiae, P. pastoris) or human cell lines (CHO, HEK).

• Experience with cell/strain engineering, with a general understanding of protein trafficking, DNA replication, and/or transcription in eukaryotic cells being a benefit.

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