14TSB_SynBio: BaseHunter: a software tool for synthetic biology procurement

Lead Research Organisation: Imperial College London
Department Name: Bioengineering

Abstract

Proteins are encoded into DNA using four chemical bases (A, T, C and G). A string of three bases is called a codon. Since
DNA has four bases, a maximum of 64 (4x4x4) unique codons can be formed. Of the 64 possible codons, 61 are used to
encode amino acids. There only 20 different amino acids used to construct proteins. Rather than having unused codons,
life uses a system in which an average of three different codons encode the same amino acid. Consequently, the same
protein sequence can be encoded with many different DNA sequences. Each DNA sequence will vary with respect to
parameters such as translational efficiency, transcriptional efficiency, protein folding and ease of synthesis. Codon
optimisation is an algorithmic process that seeks to pick the best possible variant for a given purpose. The research part of
this project seeks to develop a way of measuring how well different codon optimisation algorithms perform. This will be
done by obtaining different codon optimised genes and measuring how they behave in living systems.

Technical Summary

Proteins are encoded into DNA using four chemical bases (A, T, C and G). A string of three bases is called a codon. Since
DNA has four bases, a maximum of 64 (4x4x4) unique codons can be formed. Of the 64 possible codons, 61 are used to
encode amino acids. There only 20 different amino acids used to construct proteins. Rather than having unused codons,
life uses a system in which an average of three different codons encode the same amino acid. Consequently, the same
protein sequence can be encoded with many different DNA sequences. Each DNA sequence will vary with respect to
parameters such as translational efficiency, transcriptional efficiency, protein folding and ease of synthesis. Codon
optimisation is an algorithmic process that seeks to pick the best possible variant for a given purpose. The research part of
this project seeks to develop a way of measuring how well different codon optimisation algorithms perform. This will be
done by obtaining different codon optimised genes and measuring how they behave in living systems.

Planned Impact

Gene synthesis prices are artificially elevated because they include the cost of associated services that vendors cannot sell
in isolation. This phenomenon is most commonly seen in the coupling of gene synthesis and codon optimisation services.
Almost every vendor claims to offer the very best codon optimisation service but in the absence of comparable
performance metrics these assertions have little real meaning. To tackle this problem, we will develop a standardised
experimental protocol for quantitatively measuring algorithm quality. The resulting characterisation data will be
disseminated through our online synthetic gene procurement tool. This output will enable gene synthesis and codon
optimisation services to be priced and marketed separately. This improved pricing model will accelerate the maturation of
both technologies. In addition, enabling researchers to rationally select codon optimisation services will lead to efficiency
savings in the 'design' stage of the synthetic biology engineering cycle.

Publications

10 25 50
 
Description An improved method of synthesising DNA sequences with increased flexibility of degenerate pair positioning
Exploitation Route The associated company LabGenius Ltd, has incorporating this into a product called EVA™?. This is initially being deployed to develop novel antibody fragments in therapeutic areas where there is a distinct advantage over traditional antibody formats. EVA™? engineers high-value protein drug properties that currently remain a challenge, such as protease stability and tissue penetration, while maintaining high therapeutic potency. This next generation antibody therapies will be delivered to the human body in unprecedented ways, including orally and topically.
Sectors Agriculture

Food and Drink

Chemicals

Manufacturing

including Industrial Biotechology

Pharmaceuticals and Medical Biotechnology

URL https://www.labgeni.us/#technology
 
Description On the basis of this award an associated company, LabGenius has been founded and has now attraced over $12m of Venture Funding
First Year Of Impact 2017
Sector Agriculture, Food and Drink,Chemicals,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Title Synthetic DNA libraries 
Description The research tools developed in this study have been used to accelerate protein evolution studies (for antibodies and enzymes) across industry and academia. 
Type Of Material Technology assay or reagent 
Year Produced 2016 
Provided To Others? Yes  
Impact Researchers across industry and academia have been able to engineer novel biological components faster. 
 
Title LabGene 600 
Description A library of Synthetic DNA sequences, with synthesis information and cost. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Will act as one-stop shop for DNA synthesis to enable Synthetic biologists to readily construct their designs. 
URL http://static1.squarespace.com/static/55c8b52be4b0458b28cfaaeb/t/565ee31ce4b0b21fd7e228ff/1449059118...
 
Description Advanced materials partnership 
Organisation LabGenius
Country United Kingdom 
Sector Private 
PI Contribution - This study has resulted in the formation of a multi-lateral research collaboration between the SME (LabGenius), SynbiCITE (Imperial) and a FTSE 250 multinational operating in the advanced materials space.
Collaborator Contribution - Advancing synthetic biology with library synthesis for the development of novel advanced materials
Impact - Development of a spin out lab for the development of novel advanced materials at the industrial partner's central research facility.
Start Year 2016
 
Title COMPOSITIONS AND METHODS FOR POLYNUCLEOTIDE ASSEMBLY 
Description Methods are provided for assembly of a target polynucleotide sequence comprising at least a first double stranded polynucleotide (DSP) and at least second DSP, and optionally further DSPs. The method comprises an assembly reaction comprising steps including providing a first single stranded polynucleotide (SSP) comprising the polynucleotide sequence of one strand of the first DSP, and a second SSP comprising the polynucleotide sequence of one strand of the second DSP and converting the SSPs to double stranded form via a primer and polymerase-mediated extension reaction. The DSPs comprise polynucleotide sequences that are complementary to other polynucleotide sequences within the assembly reaction such that the ordering and directionality of each of the first and second, and further DSPs is determined by unique overhang pairing. Nucleic acid libraries and methods of making such libraries are also provided. 
IP Reference WO2017046594 
Protection Patent application published
Year Protection Granted 2017
Licensed No
Impact Spin-out LabGenius raised seed funding
 
Title DNA assembly software 
Description Software to streamline the DNA assembly process was developed as part of this project. 
Type Of Technology Software 
Year Produced 2016 
Impact Software enables the SME with which the collaboration was conducted to rapidly build novel DNA constructs. 
 
Title EVA 
Description EVA - an autonomous AI-driven evolution engine for the discovery of high-value protein components 
Type Of Technology Software 
Year Produced 2017 
Impact Assists Synthetic Biology 
 
Company Name LabGenius 
Description LabGenius develops DNA library synthesis technology and leverages this technology in a number of industrial collaborations. 
Year Established 2012 
Impact A one-stop shop for DNA assembly. An improved assembly method. In Oct 2019 LabGenius Ltd raised a $10m investment (https://www.forbes.com/sites/gemmamilne/2019/10/23/new-breed-of-biotech-investors-show-their-hand-with-10-million-investment-in-london-startup-labgenius/#1498232c71f1). LabGenius named as one of the hottest start-ups in London by Wired Magazine. https://www.wired.co.uk/article/best-startups-in-london-2019
Website http://www.labgeni.us
 
Description Engineering Biology 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Podcast in Harvard Business Review
Year(s) Of Engagement Activity 2019
URL https://hbr.org/podcast/2019/08/engineering-biology
 
Description Lecture at the Royal College of Art 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact 55 RCA students attended the lecture which was held at the RCA. The talk sparked questions and discussion afterwards, and the RCA reported increased interest in synthetic biology as a result.
Year(s) Of Engagement Activity 2016
 
Description Milken Institute 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Think Tank sponsored debate on 'Artificial Intelligence Advances, and the Ethical Choices Ahead'
Year(s) Of Engagement Activity 2019
URL https://milkeninstitute.org/videos/artificial-intelligence-advances-and-ethical-choices-ahead
 
Description RAAIS Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk at Major AI conference h(ttps://www.raais.org/raais)
Year(s) Of Engagement Activity 2019
URL https://www.youtube.com/watch?reload=9&v=yIntSV8PL5k
 
Description Synthetic Biology Commercial Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Talk on Exploring sequence space with synthetic DNA libraries at Synbiobeta San Francisco -
Year(s) Of Engagement Activity 2015
URL http://synbiobeta.com/conferences/synbiobeta-san-francisco-2015/
 
Description Ted Talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Ted Talk on TEDMED - titled 'What if machines could engineer life?'
Year(s) Of Engagement Activity 2017,2018
URL https://www.youtube.com/watch?v=FNK8ii35sHQ