Gene synthesis is rapidly transforming biomedical research. It's important to understand the current state of the marketplace to leverage the power of this technology. We reviewed the main gene synthesis companies.
What is gene synthesis?
Gene synthesis services are rapidly becoming a crucial part of modern biological research workflows. Gene synthesis or DNA synthesis is the production of gene-length double-stranded DNA fragments. Gene synthesis is different from PCR or cloning because the process is rooted in the chemical synthesis of oligonucleotides. It makes it possible to produce DNA molecules that don't exist naturally in living organisms.
Gene synthesis is not new. The first gene was synthesized in 1970 as part of an effort to decrypt the genetic code. However, this technology has been available as a service since the early 2000. Blue Heron and DNA2.0 (now ATUM) were among the first companies to provide commercial gene synthesis services. Today, gene synthesis is used to make plasmids designed in computers, optimize gene expression, and numerous other applications.
Since then, a myriad of gene synthesis companies have emerged. While any molecular biologist can make synthetic genes from oligonucleotides, commercial services have shorter turnaround times and are more cost-effective than any in-house solution.
In this review, we focus on the two main custom gene synthesis services. Sequence-verified clones and double-stranded DNA fragments that are not sequence-verified. The latter must be inserted by the users into the cloning vectors of their choice.
There are now so many companies providing DNA synthesis services that it can be difficult to identify the right partner. This is a list of GenoFAB's top 5 gene synthesis companies in 2020.
The Pioneer: Integrated DNA Technologies
Integrated DNA Technologies also known as IDT is a well-respected name in the molecular biology community. They were founded in 1987 in Coralville, Iowa. They initially specialized in the synthesis of oligonucleotides. They now largely dominate the oligo synthesis market. Many molecular biologists have ordered primers for PCR and Sanger sequencing from IDT.
The growing demand for gene synthesis services provided them with a growth opportunity that took advantage of their core expertise in oligo synthesis. Initially, they only offered the synthesis of small genes. They were also the first to offer dsDNA fragments that they sold under the commercial name of gBlocks.
Today, they provide a very comprehensive suite of DNA synthesis services. In particular, they offer DNA fragments up to 3kb in length. They can generate fragment libraries by mixing bases in different positions. They offer standard gene synthesis services for fragment up to 5kb in length. They also offer specialty services like DNA origami and ssDNA fragments up to 500 bp.
Their website includes a number of bioinformatics tools, including a codon optimization application.
The Shooting Star: Twist Biosciences
Twist Biosciences took the world of gene synthesis by surprise. Founded in 2013, it rapidly developed a proprietary technology by miniaturizing the oligo synthesis and gene assembly processes. This gave this startup a competitive advantage by increasing its throughput and reducing cost. After raising more than $250M, the company went public in 2018 and its capitalization is now exceeding $1bn.
Twist is very focused on gene synthesis. They provide both clonal genes and gene fragments. They have fast turnaround times and the most competitive prices on the market. For a few years, they have been setting up the gene synthesis standards that many competitors are trying to match. In partnership with Microsoft, Twist has been aggressively developing the emerging market of DNA data storage.
Twist has a modern software infrastructure that makes it easy for users to place orders. They are the only company providing an API.
The DNA Printer: Codex
Codex is the new name of SGI-DNA, the DNA synthesis arm of Synthetic Genomics. This company has its roots in the ground-breaking research of the J. Craig Venter Institute in synthetic biology.
Codex business model is unlike any other in the DNA synthesis world. They provide both gene synthesis services like their main competitors. They also provide a gene synthesis instrument and DNA assembly reagents.
This multiplicity of offers can be confusing. In particular, the benefits of their BioXp™ 3200 instrument is less than obvious. To synthesize specific gene sequences, users of the BioXP system need to order sequence-specific DNA cartridges. Within 3-5 days, cartridges containing pieces of desired genes arrive ready to load into the machine. Within a few hours, experiments can progress with transfection-ready DNA.
At the end of the day, the turnaround time does not seem much faster than commercial gene synthesis service. This makes it difficult to justify the investment in an expensive piece of equipment.
Codex core expertise lies in its proprietary DNA assembly technology more than its DNA synthesis itself. They are the partner of choice for complex projects that involve unusually complex DNA assembly steps.
The Generalists: Eurofins and GenScript
Most gene synthesis services are provided by Contract Research Organizations (CROs). These organizations provide broad ranges of research services that include DNA sequencing, protein expression and purification, genotyping, and many others. Eurofins and GenScript are good illustrations of this category of gene synthesis service providers.
In just over 30 years, Eurofins has grown from one laboratory in Nantes, France to over 47,000 staff across a network of more than 900 independent companies in over 50 countries, operating more than 800 laboratories. Performing over 400 million tests every year, Eurofins offers a portfolio of over 200,000 analytical methods to evaluate the safety, identity, composition, authenticity, origin, traceability and purity of biological substances and products, as well as providing innovative clinical diagnostic testing services, as one of the leading global emerging players in specialised clinical diagnostics testing. Eurofins is one of the fastest growing listed European companies. Since its IPO on the French stock exchange in 1997, Eurofins’ sales have increased by 35% each year (in compound average) to over EUR 4.5 billion in 2019.
Founded in 2002 and listed on the Hong Kong Stock Exchange in 2015, GenScript has an established global presence across Greater China, North America, the EU, and Asia Pacific. GenScript provides a comprehensive service portfolio that includes custom reagent services, antibody drug development services, and catalog products. Their reagent services include custom gene synthesis and molecular biology, custom protein expression and purification, custom peptide synthesis, antibody production, and custom cell line development. GenScript currently has more than 3000 employees globally and an annual revenue of $250M.
Because gene synthesis is not the core business of CROs like GenScript and Eurofins they tend to provide commodity services. Their prices can be very competitive because of economies of scale and because they can offshore the most labor-intensive part of the gene synthesis process. For large companies that need a number of different contract research services, it may be advantageous to work with a single vendor who can provide many of these services rather than managing a network of more specialized service providers.
All the companies who are currently providing commercial gene synthesis services are relying on the solid phase synthesis of oligonucleotides. A new generation of gene synthesis companies are betting the enzymatic synthesis of DNA molecules. The companies leading this charge include San Diego-based Molecular Assemblies, Ansa Biotechnologies, and Paris-based DNAScript.
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