TechSprouts is a platform to engage with the deep science ecosystem in India

TechSprouts Monthly: May 2023

The outlook on DNA Synthesis, updates on new Centres of Excellence and more

Image courtesy DALL.E 2

Content from TechSprouts

  1. Synthetic Biology: Transforming the Industrial Chemicals Space
  2. Synthetic Biology: Winds of change in agriculture

Deep science funding updates

  • ImmunoACT, which is developing an affordable CAR T-cell therapy for blood cancer treatment, received $10 million in funding in a Series B round as Laurus Labs increased its stake in the company to 33.86%.
  • NewTrace manufactures innovative electrolyzers for hydrogen production, and raised $5.6 million in a seed funding round led by Sequoia Capital India.
  • Smart cold storage container startup Tan90 raised a seed round of $1.4 million with participation from Blue Ashva Capital and Capital-A among others. Tan90’s solutions utilize phase-change materials for off-grid cooling.
  • Chennai-based fabless semiconductor startup InCore Semiconductors raised a seed round of $3 million led by Sequoia Capital to scale up its operations in the RISC-V based SoC space.

Deep science ecosystem updates

  • The Indian Space Research Organisation (ISRO) successfully placed NVS-01, the first of its second-generation satellites, into geosynchronous orbit.
  • C-CAMP, Bangalore, received CSR funding from global biotech company Cytiva. This funding will be used for support and scale-up of early-stage biotech startups.
  • IIT Madras has launched 15 Centres of Excellence as part of the Institute of Eminence (IoE) scheme to undertake research and develop cutting-edge technologies. These centres are interdisciplinary and the subjects include emergent materials, integrated circuits, low carbon construction, to name a few.
  • A day-long exhibition showcasing the impact of Public-Private collaborative funding under the IMPacting Research INnovation and Technology (IMPRINT) II Scheme was held in May. These projects consisted of public-private partnerships where academia and industry worked together from the outset.

News from the research community

Deep Science Thoughts

DNA Synthesis-Challenges and Opportunities

Rob Carlson in 2003 predicted that the doubling time of DNA sequencing and synthesis technologies would be at least as fast as Moore’s law and would also drive down the costs of these technologies. What came to be known as Carlson Curves, the predictions have proved to be true and more. The costs of reading/sequencing DNA/RNA have been falling significantly over the past two decades, especially with the advent of faster parallel sequencing technologies such as Next Generation Sequencing (NGS). Today, a complete human genome sequencing can be done in less than $1000 within 24 hours, a drop from more than $100 million requiring a few months at the beginning of the century. This has meant availability of huge data sets on microbial, humans as well as other animal/plant genomics which can be analysed and used for biotechnology applications.

Nucleotide synthesis, on the other hand, has progressed at a slower pace. Phosphoramidite synthesis, the technology used generally for DNA synthesis was developed in the 1980s. Although it is an efficient technology, it faces two major limitations: use of highly unstable toxic chemicals (stability of one or two weeks) which makes the process costly when the synthesizers are operated for longer time periods. Secondly, the accuracy of the technology becomes questionable for synthesizing longer chain DNA. Despite the fact that the accuracy of adding individual nucleotides to the chain would be more than 99.6%, even the minute errors can have a significant impact on the final sequence generated. These two factors put together have limited the maximum length of DNA sequenced to 200–300 base pairs.

Most of the applications of synthetic DNA currently are limited to short chain sequences such as primers for therapeutic and diagnostic purposes, due to limitations in the synthesis of long chain synthetic DNA. However, things are starting to change. Several companies have emerged with innovative enzymatic processes for long chain DNA synthesis. These include the likes of Twist Bioscience, DNA Script, Evonetix, Nuclera, Ribbon Biolabs, Camena Bioscience, Molecular Assemblies, Ansa Biotechnologies and GenScript. These companies are leading the charge in making DNA synthesis affordable and accessible at the lab benchtop. They are targeting applications in designing new drugs, textiles, improved crops, DNA data storage and many more. DNA Script launched its desktop DNA printer in 2021 and has gone on to raise more than $200 million in January 2022. The company is also launching the most advanced fully automated version of its device which can synthesize an oligo up to 120 nucleotides long in under 24 hours. Similarly, Twist Bioscience launched its enzymatic DNA synthesis kit in January 2022. Currently, most of these products are based on a terminal deoxynucleotidyl transferase, or TdT enzyme which has been engineered to make the nucleotide synthesis affordable and faster. However, it is still early days and enzymatic DNA synthesis will require some time before it becomes a standard in the market.

While the demand for synthetic DNA has increased over the years, the cost of synthesizing per base has fallen equally fast. Overall, the value of the market has not grown much in these years, in contrast to the transistor market which is always a standard for comparison. The main reason behind this is the fact that you only require one copy of the synthetic DNA which can be used to produce millions of copies naturally using microbial systems, thereby limiting the market demand for synthetic DNA. On the other hand, every transistor sold needs to be synthesized independently and thus the market has seen tremendous growth over the years. DNA synthesis is likely to remain a difficult business until there is a revenue model in which the final value of the product depends on the actual number of bases synthesized and sold, for example in DNA Storage.

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TechSprouts is a platform to engage with the deep science ecosystem in India