In-silico tools for efficient genome editing

The discovery of restriction endonucleases and DNA ligases in the early 1970s was a turning point for biology. These enzymes are the scissors and glue for working with genetic material, respectively, and enabled researchers to edit genomes for the first time in history. Genes from one organism could now be cut and pasted into the genome of another, giving rise to modern biotechnology. The protocols have been standardized since then for popular model organisms, but synthetic biology aims higher.There’s still much room for improvement in the efficiency of the techniques used in genetically modifying organisms. In addition, the repertoire of engineerable organisms has the potential to open up many new applications. Accomplishing these goals is a major challenge for biotechnology, fortunately, in-silico genetic engineering is a probable solution. A host of companies now provide in-silico tools for efficient genome editing. One such company is the Desktop Genetics (@DesktopGenetics), a UK based startup.

Simplifying cloning

Desktop Genetics was founded by Riley Doyle, Victor Dillard and Edward Perello. The trio won the Cambridge University Entrepreneurs competition that gave them the push to start their venture right after university in the summer of 2012. The team developed a bioinformatics platform, AutoClone, that is used for researchers engaged in synthetic biology.Researchers can upload their sequences and input their desired sequences. The DNA search engine then comes up with a protocol to perform the cloning. It allows for optimal design, synthesis, management, and sharing of DNA constructs. The core platform can be customized to suit the needs of a spectrum of companies working in various sub-disciplines of genetic engineering. These involve gene expression, antibody engineering, cell line development, functional genomics, gene editing, and protein production.The startup has teamed up with Horizon Discovery to work on what the MIT Technology Review heralded as the biggest biotech breakthrough of the century.

Genomic cruise missiles

The monumental discovery was how an elegant defence system in bacteria, the CRISPR/Cas9 system, could be hacked to engineer organisms. It is a form of acquired immunity that helps bacteria to fight viruses and foreign plasmids. CRISPRs are clustered, interspaced, palindromic repeat sequences which are associated with the Cas family of genes. The system stores a portion of foreign DNA within the CRISPR sequence that is used as a quick guide to diagnose it during subsequent infections.

The process can be mimicked by introducing Cas9 protein and guide RNAs to make an edit at any desired location in the genome with extreme precision. Many genome editing breakthroughs have been made by utilizing it over the last three years. Notable among these have been reversal of symptoms of a liver disorder in mice and genome engineering of rice. Harvard University holds the patent for CRISPR, though in a hotly debated ownership between University of California and University of Vienna.Horizon is another UK company that uses its technologies in translational genomics to develop improved drug discovery and diagnostic tools. It licensed the technology from Harvard in September 2013. Horizon’s kitty of gene editing technologies also includes retroviral vectors and zinc finger nucleases. However, CRISPR seems to function more precisely than other current alternatives for editing genomes. It is comparatively easier to generate large vector libraries using CRISPRs and multiple sites can be targeted simultaneously.

Riding the CRISPR wave

Desktop Genetics is not the first company to offer ability to edit genomes on your computer, but it does two things differently. Firstly, in a time when even hardware is being built open source, the startup offers a paid, proprietary software package. The team is betting on the researchers preferring quality and security over cost here. Second, is its focus on CRISPRs. This has the potential to pay greater dividends, considering the prevailing enthusiasm in the industry for the technology.Startups have come up, backed with solid fundings, to chart the commercial potential of CRISPR based therapies. These include Editas Medicine, CRISPR Therapeutics, and Intellia Therapeutics. Caribou Biosciences is another startup that is taking a more diverse approach in target applications. Of these companies, three were co-founded by the disputed owners of the patents on CRISPR. Feng Zhang (Editas) was awarded the patent on human applications of CRISPR, something which was an obvious implication of work done by Doudna (Caribou) and Charpentier (CRISPR Therapeutics) on the other.All of this excitement surrounding CRISPRs has rekindled hopes for corrective gene therapy for the treatment of diseases, such as haemophilia. The success of these early companies will determine how long it takes for us to achieve those goals. Meanwhile, being able to efficiently edit genomes on your computer will contribute significantly to newer applications in synthetic biology.