Manipulation of tRNA to Enhance Biologic Production

Lead Research Organisation: University of York
Department Name: Biology

Abstract

Biologic production is a multibillion dollar industry, providing substantial healthcare benefits and unlimited opportunity for expansion. Funded by a BBSRC Industrial Biotechnology Catalyst Early Stage Translation Award, my lab developed a novel synthetic biology strategy that boosts product quality and yield in proof-of-principle experiments. Follow-on funding is sought to support conclusive tests of our strategy using proprietary platforms and biologics under conditions of industrial production, in collaborations with multinational companies.

Our strategy is based on measuring and manipulating tRNAs required for biologic synthesis. Some tRNAs are much more abundant than others and scarcity of a single tRNA can restrict production. However, relative levels of tRNAs have not been measured in industrial contexts. We propose to fill this key knowledge gap and remediate deficiencies by tRNA supplementation and improved codon optimization.

Publications

10 25 50
 
Description We have found a significant depletion of tRNA when bioreactors are used to produce biopharmaceuticals. Not all tRNAs are depleted equally and a minority buck the trend completely. The changes are likely to hamper productivity.
Exploitation Route Steps can be taken to restore tRNA expression &/or to adapt codon usage for better use of limiting tRNAs
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Optimisation of CHO for Biotherapeutic Manufacture
Amount £3,608,961 (GBP)
Funding ID EP/V038095/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 09/2021 
End 09/2026
 
Description FDBK studentships 
Organisation Fujifilm
Department Fujifilm Diosynth Biotechnologies, UK
Country United Kingdom 
Sector Private 
PI Contribution White, Bryant & Ungar as supervisors and co-supervisors
Collaborator Contribution Studentships awarded to FDBK as a Collaborative Training Partnership.
Impact No outputs yet
Start Year 2020
 
Description Fujifilm Diosynth Biotechnologies Centre of Excellence in Bioprocessing 2.0 
Organisation Fujifilm
Department Fujifilm Diosynth Biotechnologies
Country United States 
Sector Private 
PI Contribution I lead the bid from University of York to join this partnership
Collaborator Contribution My staff have been conducting tests in FDB laboratories, using their equipment and reagents
Impact Ongoing.
Start Year 2019
 
Description Prosperity Partnership 
Organisation Fujifilm
Department Fujifilm Diosynth Biotechnologies, UK
Country United Kingdom 
Sector Private 
PI Contribution We are actively contributing to four of the five work packages.
Collaborator Contribution FDBK are the Industrial partners. Additional academic partners are the universities of Edinburgh (lead) and Manchester.
Impact No outputs yet.
Start Year 2021
 
Description Fujifilm Diosynth Biotechnologies Centre of Excellence in Bioprocessing 2.0 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact Ongoing collaboration involving industrial partner Fujifilm Diosynth Biotechnologies UK and the Universities of Edinburgh, Manchester and York.
Year(s) Of Engagement Activity 2019,2021,2022