Since the discovery of DNA in the mid-19th century and the complete sequencing of the human genome in 2003, genome (or gene) editing has made great strides in the biological field. A decade later in 2015, scientists and later Nobel Prize winners Emmanuelle Charpentier and Jennifer Doudna pioneered the revolutionary gene editing technique CRISPR. CRISPR gene editing uses an enzyme that works like molecular scissors to alter/edit targeted sections of DNA and turning genes on or off without altering their sequence (1).
“The ability to cut DNA where you want has revolutionized the life sciences,” said Pernilla Wittung Stafshede, member of the Nobel chemistry committee. Clinical trials are under way to use the technique to treat sickle- cell -anaemia, hereditary blindness, and cancer. The two scientists along with others in the field, have launched a generation of biotechnology companies focused on developing techniques to achieve these goals (2).
The emergence of a new method
With dozens of clinical trials currently in progress, CRISPR is just getting started. Meanwhile one company is making its way to rewrite the future of genetics disease. Tessera Therapeutics, a Massachusetts based biotechnology start-up has spent the past few years developing a new class of ‘molecular manipulators’ capable of doing lots of things CRISPR can do and some that it can’t. They call this methode ‘gene writing’. Despite CRISPR’s therapeutic potential, the technology does have its limitations. It is useful for deleting problematic genes, but it is less effective at replacing them. This means that only certain inherited conditions can be treated this way (3). It is also better suited for editing genes in the lab, outside the body, than in living organisms (4). The possibility of editing (or rather writing) genes resulted in a team of researchers led by Harvard to successfully treat sickle cell disease in mice. This advancement could one day lead to a possible cure of the deadly inherited blood disorder that affects more than 300,000 newborns each year (5).
“DNA being the code of life as we know it, the opportunity to be able to make modifications with very high precision to a subset of cells in your body is going to be applicable to diseases in every therapeutic area,” said Tessera CEO Geoffrey von Maltzahn. The gene writing approach is based on mobile genetic elements, or MGEs, a class of genes that turns out to be the most abundant category of genes in nature (6). Recent work reveals that many organisms use MGEs for specialized functions, one that depends on its ability to move around the genome and modifying the DNA sequence in the process (7).
To accelerate its development, Tessera attracted over $230 million in financing in 2020 (8). This surely contributes to Tessera’s mission of delivering on the full potential of genetic medicine. This investment indicated genuine interest in the potential gene writing and will accelerate the company’s ability to position multiple therapeutic programs for clinical development. Using computational and high-throughput laboratory platform has enabled the team to design, build, and test thousands of engineered and synthetic MGEs for writing and rewriting the human genome.
RNA-based gene writing could go where CRISPR-based editing can’t and one day Tessera hopes will surmount the limitations of gene editing and gene therapy and cure genetic diseases by rewriting DNA.
References
1. https://www.aamc.org/news-insights/conversation-jennifer-doudna-phd-developer-crispr-gene-editing-technology
2. https://www.nature.com/articles/d41586-020-02765-9
3. https://www.pharmaceutical-technology.com/features/gene-writing-future-genetic-medicine/
4. https://www.freethink.com/science/gene-writing
5. https://news.harvard.edu/gazette/story/2021/06/gene-editing-shows-promise-as-sickle-cell-therapy/
6. https://www.fiercebiotech.com/biotech/tessera-therapeutics-scores-230m-to-ramp-up-gene-writing-tech-to-cure-disease
7. https://www.geneonline.com/tessera-therapeutics-aims-to-rewrite-dna-with-new-age-gene-manipulators/
8. https://www.bloomberg.com/press-releases/2021-01-12/tessera-therapeutics-attracts-over-230m-in-series-b-financing-to-advance-gene-writing-a-new-category-in-genetic
