DNA synthesis & gene foundry

01Overview and value chain

Markers: [EC: HHS/IGSC gene-synthesis sequence screening guidance | OECD: Genomics & bioinformatics | Regulator: FDA (USA), EMA (EU), NMPA (China)]

DNA synthesis and the gene foundry are the “write-and-build” service layer of synthetic biology: a researcher designs a sequence on a computer and a service provider chemically synthesises the gene, clones it and ships it back, or builds the whole strain through a Design-Build-Test-Learn (DBTL) foundry loop. The established chemistry is phosphoramidite synthesis, which adds bases one at a time to a growing chain but is capped at roughly 200 to 300 nucleotides per oligo; genes are then assembled enzymatically into fragments up to about 3000 base pairs (IDT gBlocks) and beyond. Cost has collapsed from about one dollar per base in the early 2000s to a few cents per base today, and Twist Bioscience’s silicon-based platform parallelises thousands of genes on a single wafer. The next frontier is enzymatic synthesis, in which terminal deoxynucleotidyl transferase (TdT) adds natural bases without harsh acid, promising longer, cleaner oligos — the basis of DNA Script’s SYNTAX printer. Because anyone can now order the DNA of dangerous pathogens, the International Gene Synthesis Consortium (IGSC) screens around 80 percent of global commercial gene synthesis against regulated-pathogen sequences.

The key directions of DNA synthesis and the gene foundry are:

1. Phosphoramidite gene synthesis (Phosphoramidite Gene Synthesis): the established oligo-to-gene-to-clone service chain behind IDT, Twist, GenScript, Eurofins and BGI, delivering genes of a few thousand base pairs in days.
2. Enzymatic DNA synthesis (Enzymatic DNA Synthesis): template-independent polymerases such as TdT add natural nucleotides in water, the next-generation chemistry behind DNA Script’s SYNTAX printer, promising longer oligos without acid deprotection.
3. Biofoundry DBTL operations (Biofoundry DBTL): automated Design-Build-Test- Learn loops that turn synthesised genes into assembled constructs and engineered strains (Asimov CAD, Synthace automation, Ginkgo Bioworks foundry).
4. Sequence-screening biosecurity (Sequence Screening): IGSC and HHS-aligned customer- and sequence-screening protocols that block orders matching regulated- pathogen sequences, the biosecurity gate on the whole industry.

Sectoral value chain

[digital DNA design] ──> [oligo synthesis] ──> [gene assembly & cloning] ──> [sequence verification]
                                             │
                                  (IGSC pathogen screening)
                                             │
                                             ▼
[strain build] <─── [DBTL foundry] <─────┘

Value chain levels

Cross-cutting technologies of the sector:

• Phosphoramidite chemistry (Phosphoramidite Chemistry): the four-step base-addition cycle (detritylation, coupling, capping, oxidation) running on automated solid-phase synthesizers.
• Silicon-parallelised oligo synthesis (Silicon-Parallelised Synthesis): Twist’s semiconductor-style micro-well array writing thousands of oligos per wafer.
• Foundry automation & CAD (Foundry CAD): liquid-handling robots, cloud LIMS and design software (Asimov, TeselaGen, Synthace) running the DBTL loop unattended.

02US

The United States hosts the three largest commercial gene-synthesis providers and the leading next-generation enzymatic-synthesis and foundry-software companies.

gene-synthesis leaders, enzymatic synthesis, foundry CAD

• Integrated DNA Technologies (IDT): founded in 1987 in Coralville, Iowa, IDT is the original innovator in gene fragments, supplying gBlocks (to ~3000 bp), xGen NGS capture probes and a full cloning and mutagenesis service.
• Twist Bioscience: its silicon-based platform parallelises gene synthesis across thousands of micro-wells per wafer, and Twist has expanded its clonal-genes and NGS offerings through 2026.
• GenScript: a global gene-synthesis and molecular-biology service provider, GenScript delivers gene synthesis, cloning and mutagenesis alongside its ProBio CDMO arm.
• DNA Script: founded in 2014, DNA Script commercialises enzymatic DNA synthesis on its SYNTAX benchtop printer using engineered TdT, moving synthesis from centralised factories toward the bench.

03CN

China’s gene-synthesis capacity is anchored by BGI and a growing cluster of domestic providers serving both the domestic research market and international customers.

domestic synthesis capacity, biosecurity law, scale

• BGI (华大基因): a global genomics and gene-synthesis organisation offering DNA oligo and gene-synthesis services alongside its sequencing dominance, with capacity scaled to high-throughput domestic and international research demand.
• Biosecurity compliance: China’s biosecurity law (2021) requires customer and sequence screening for gene-synthesis orders, aligning domestic providers with the IGSC framework.
• Domestic cluster: a layer of specialist oligo and gene-synthesis firms serves Chinese universities and biotech, increasingly price-competitive on routine genes.

04EU

Europe’s gene-synthesis market is led by the Eurofins Genomics platform and a strong foundry and design-software base.

Eurofins genomics, design software, distributed foundries

• Eurofins Genomics (Ebersberg, Germany): the Eurofins gene-synthesis and oligo arm is a major European provider of custom DNA, gene synthesis and next-generation-sequencing services for academic and industrial customers.
• Design and automation software: European and US-foundry software (TeselaGen, Synthace) increasingly coordinates distributed biofoundries running the DBTL loop.
• Standards alignment: EU gene-synthesis providers participate in IGSC screening and EMA-relevant GMP workflows where synthesised genes enter pharmaceutical development.

05Leading companies and research institutes

06Tech stack and innovations

The gene-synthesis and foundry stack rests on three generations of chemistry plus cloud-coordinated automation, each widening access to written DNA.

1. Phosphoramidite solid-phase synthesis (Phosphoramidite Synthesis):
   • the four-step cycle (detritylation, coupling, capping, oxidation) adds a base every few minutes on controlled-pore-glass supports, capped near 200 to 300 nucleotides per oligo.
   • genes to about 3000 base pairs are then assembled enzymatically from overlapping oligos (IDT gBlocks) and cloned into vectors.
2. Silicon-parallelised synthesis (Silicon-Parallelised Synthesis):
   • Twist replaces column synthesis with a silicon micro-well array, writing thousands of oligos per wafer and cutting per-gene cost.
   • the parallel oligo pool is assembled, amplified and verified into clonal genes.
3. Enzymatic TdT synthesis (Enzymatic TdT Synthesis):
   • engineered terminal deoxynucleotidyl transferase (TdT) adds natural nucleotides in aqueous buffer without acid deprotection, promising longer and cleaner oligos.
   • DNA Script’s SYNTAX printer brings enzymatic synthesis to the benchtop, decentralising gene synthesis.

07Value chains and production pipelines

Industrial pipeline of a synthesised gene (IGSC-screened)

┌───────────────────────────┐      ┌───────────────────────────┐
│ 1. Digital DNA design     │ ───> │ 2. Oligo synthesis        │
└───────────────────────────┘      └───────────────────────────┘
                                                  │
                                                  ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 4. Sequence verification  │ <─── │ 3. Gene assembly + cloning│
└───────────────────────────┘      └───────────────────────────┘
              │
              ▼
┌───────────────────────────┐      ┌───────────────────────────┐
│ 5. DBTL strain build      │ ───> │ 6. Screening + delivery   │
└───────────────────────────┘      └───────────────────────────┘

Stage 1: Digital DNA design

The customer’s desired protein is reverse-translated, codon-optimised for the expression host and split into overlapping oligo designs in CAD software (Asimov, TeselaGen).

Stage 2: Oligo synthesis

Overlapping oligos of roughly 200 to 300 nucleotides are synthesised base-by-base by phosphoramidite chemistry (or enzymatic TdT on the SYNTAX printer), cleaved and deprotected.

Stage 3: Gene assembly and cloning

The oligo pool is assembled by polymerase cycling assembly into the full gene, amplified by PCR, and cloned into the chosen vector by ligation-independent or restriction cloning.

Stage 4: Sequence verification

The cloned gene is checked by Sanger or next-generation sequencing against the design, and any synthesis errors are corrected before release.

Stage 5: DBTL strain build

In a foundry, the verified construct is transformed into the production host, colonies are screened by automation, and the DBTL loop iterates expression and titre until the strain meets specification.

Stage 6: Screening and delivery

Before fulfilment, the order is screened against regulated-pathogen sequences under IGSC/HHS protocols, then QC-released and shipped to the customer as a verified gene, clone or engineered strain.