Marvin Tanenbaum | Professor
Hubrecht Institute

Festival of Biologics Day 2 @ 17:10

Beyond the Kozak sequence: an extended translation initiation sequence (eTIS) for higher-yield, higher-fidelity protein expression

Expression platforms optimize vectors, host cells, UTRs and codon usage, yet translation initiation, a rate-limiting step in protein synthesis, is still guided by the 40-year-old Kozak consensus sequence, a short sequence flanking the start codon. Here, using massively parallel reporter assays, machine learning and high-resolution structural analysis, we identified a greatly improved start-codon sequence grammar: the 'extended translation initiation sequence', or eTIS. eTIS-guided mRNA design improves start-codon recognition to >99%, strongly suppresses off-target protein production and increases protein output without changing the encoded protein. Across therapeutic protein and vaccine-antigen constructs, we observe typical expression gains of 15–40%, with several-fold gains in some cases. This talk will discuss the mechanism of eTIS-driven translation initiation and how eTIS can be integrated into biologics expression workflows to improve yield and product quality.

Marvin Tanenbaum, Professor, Hubrecht Institute

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Marvin Tanenbaum / Beyond the Kozak sequence: an extended translation initiation sequence (eTIS) for higher-yield, higher-fidelity protein expression

Marvin Tanenbaum, Professor,
Hubrecht Institute

Marvin Tanenbaum is a senior group leader at the Hubrecht Institute, an Investigator at Oncode Institute, and Professor of Bionanoscience at Delft University of Technology. His laboratory studies how mRNA sequence and translation dynamics control protein production, combining advanced imaging and...

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