Cambridge genomics pioneer Constructive Bio unveils gene synthesis breakthrough

Cambridge synthetic biology pioneer Constructive Bio, which accelerated out of stealth with $15 million seed cash last year, has made significant advances with its next generation genome synthesis technology, CONEXER.

Constructive Bio is set to re-engineer biology and create completely new classes of enzymes, pharmaceuticals and biomaterials. Its proposition is predicated on commercialising the ground-breaking synthetic biology research of CSO Professor Jason Chin.

The Chesterford Research Park company holds an exclusive licence to IP developed by the Chin Lab at the Medical Research Council’s Laboratory of Molecular Biology in Cambridge.

The Chin Lab has pioneered the development and application of methods for reprogramming the genetic code of living organisms, rewriting the near-universal genetic code of natural life to create organisms that use new genetic codes.

Published in Nature, the latest paper from Jason Chin’s Lab, and led by Jérôme Zürcher, Askar Kleefeldt, Louise F. H. Funke, PhD, Julius Fredens and Jakob Birnbaum, addresses this challenge through the development of CONEXER, the next generation in genome synthesis technology. 

CONEXER combines conceptual and genetic advances to turn genome synthesis into a continuous process, massively accelerating the iteration between synthetic replacement steps. This means the implementation of 500 kbp of synthetic DNA can be achieved within 10 days.

Constructive Bio states: “Genomes provide a formula for the life of an organism – being able to write them from the bottom up constitutes a powerful approach for testing fundamental biological hypotheses, and for endowing organisms with new properties that may not be found in nature. 

“We previously demonstrated the creation of an E. coli cell with a synthetic genome, Syn61, which uses a reduced set of codons (61 as opposed to 64) to make the proteins it needs to survive. By reprogramming its genetic code, we showed that Syn61 is resistant to viral infection and has the ability to produce entirely unnatural biopolymers.

“Synthesizing a heavily modified genome and implementing it into a living cell is no easy task – it is a stepwise process, where the product of each step serves as a template for the next. 

“Our proprietary technologies for genome synthesis, REXER, GENESIS and most recently CONEXER, enable the assembly of synthetic DNA in the scale of hundreds of kbp, and the replacement of ‘natural’ DNA with its synthetic counterpart. Each step of replacement can provide valuable information about the biological functionality of a synthetic DNA sequence, but performing many steps comes at the cost of speed. 

“Accelerating the transition between steps is paramount for achieving throughput and scalability in the genome synthesis process.

“Moreover, the paper describes a complementary technology, termed BASIS, which enables the construction of heterologous megabase-scale DNA constructs as extrachromosomal episomes in E. coli. The researchers use BASIS to build a 1 Mb fragment of human DNA in E. coli, encoding the CFTR gene, and demonstrate that the construct can be successfully delivered intact into human cells. This technology sets a foundation for extending the genome building toolkit developed in E. coli for the assembly of large, synthetic DNA pieces for organisms across all walks of life.

Constructive Bio is backed by leading DeepTech investors – Ahren, Amadeus Capital Partners, OMX Ventures and General Inception.

The company is based on two core proprietary platform technologies:-

  • Large scale DNA assembly – to construct large chunks of DNA at unprecedented scale eg. whole bacterial genomes can be built from scratch
  • Genome reprogramming – to systematically recode whole genomes to engineer unnatural products for commercial applications.

Together the technologies will be used to synthesise polymers with non-natural amino acids for commercial applications across a range of industries including novel therapeutics and antibiotics, enhanced agriculture, manufacturing and materials. 

There are considerable bonuses: The strains’ phage resistance can be used to increase bio-manufacturing yields. And novel polymers can be designed with the ability to breakdown and recycle the monomers to support a circular sustainable economy, offering approaches to transform industries such as the c.$750 billion global polymers market and help overcome global challenges like climate change to benefit the planet and mankind.


Article sourced from: www.businessweekly.co.uk
Published on: 18.07.23