From reading to writing the book of life - how synthetic biology is transforming science and medicine
For decades, scientists have been extraordinary readers of life's genetic code, but a revolutionary transformation is underway—we are increasingly becoming its writers. The emergence of high-throughput DNA synthesis technologies represents a fundamental shift in our relationship with biology, enabling researchers to create artificial DNA sequences with unprecedented speed, accuracy, and scale.
This powerful capability forms the backbone of the rapidly growing synthetic biology field, which aims to design and construct new biological parts, devices, and systems 1 2 .
Imagine having a word processor for DNA—instead of merely copying and pasting existing genetic sentences, scientists can now compose entirely new ones. This technological leap is driving innovations across medicine, agriculture, industrial biotechnology, and beyond.
From personalized cancer therapies to sustainable bio-fuels, the ability to rapidly "write" DNA is accelerating scientific discovery and opening doors to solutions for some of humanity's most pressing challenges 6 9 .
The global DNA synthesis market is projected to grow from USD 3.7 billion in 2025 to USD 13.7 billion by 2035, reflecting the tremendous potential of these technologies 9 .
Projected Growth
The foundation of modern DNA synthesis was laid in the 1980s with the development of phosphoramidite chemistry and automated column-based synthesizers 2 7 . This method builds DNA strands nucleotide by nucleotide through a four-step cycle: deprotection, coupling, capping, and oxidation 7 .
Each cycle takes several minutes and achieves approximately 99.5% efficiency, meaning some molecules fail to incorporate the intended nucleotide at each step 6 .
The need for higher throughput at lower costs led to the development of microarray-based synthesis technologies. These approaches enable parallel synthesis of thousands to hundreds of thousands of unique oligonucleotides on miniature chips 1 2 .
Several innovative techniques fall under this category: photolithographic synthesis, inkjet printing, and electrochemical/thermally controlled synthesis 1 2 .
The most recent breakthrough comes from enzymatic DNA synthesis, which harnesses biological catalysts rather than harsh chemicals. This approach uses engineered versions of terminal deoxynucleotidyl transferase (TdT), a natural enzyme that adds nucleotides to DNA strands without needing a template 6 .
Companies like Ansa Biotechnologies have developed TdT-based systems where the enzyme is reversibly blocked after adding each specified nucleotide, enabling precise, stepwise synthesis of a predetermined sequence 6 .
| Synthesis Method | Key Features | Max Oligo Length | Throughput | Key Limitations |
|---|---|---|---|---|
| Column-Based | Phosphoramidite chemistry, solid support | 100-200 nt | 96-1536 reactions | Toxic solvents, length limited, error accumulation |
| Microarray | Parallel synthesis on chips | ~150 nt | Up to 500,000 spots per chip | Still uses modified chemistry, shorter products |
| Enzymatic | Aqueous, TdT enzyme-based | 750+ nt | Growing rapidly | Newer technology, still being optimized |
In 2017, a team of scientists led by Dr. Boles achieved a landmark demonstration of automated DNA synthesis with their Digital-to-Biological Converter (DBC) 2 .
This integrated system could translate digital genetic information directly into functional biological components through a fully automated process:
The DBC successfully demonstrated end-to-end automation of genetic construction, significantly reducing the time and labor required for synthetic biology workflows.
This experiment highlighted several groundbreaking capabilities:
This pioneering work established a blueprint for the automated biofoundries that are becoming increasingly common in synthetic biology research and industrial applications today.
Modern high-throughput DNA synthesis relies on a sophisticated ecosystem of reagents, enzymes, and automated systems.
| Reagent/Technology | Function | Example Applications |
|---|---|---|
| Phosphoramidites | Nucleotide building blocks for chemical DNA synthesis | Oligonucleotide synthesis for PCR primers, probes |
| Terminal Deoxynucleotidyl Transferase (TdT) | Template-independent DNA polymerase for enzymatic synthesis | Long-fragment DNA synthesis, complex sequence production |
| DNA Ligases | Join DNA fragments together | Golden Gate Assembly, NEBuilder HiFi DNA Assembly |
| DNA Polymerases | Amplify DNA fragments; proofread sequences | PCR, error correction, site-directed mutagenesis |
| Restriction Enzymes | Cut DNA at specific sequences | Golden Gate Assembly, cloning |
| Competent Cells | Host cells for transforming synthetic DNA | E. coli strains for plasmid propagation |
Systems like the Echo 525 Liquid Handler enable precise nanoliter-scale dispensing of DNA assembly reactions 5 .
Technologies like NEBuilder HiFi DNA Assembly allow efficient, seamless joining of multiple DNA fragments with high accuracy 5 .
Specialized competent E. coli cells in 96-well and 384-well formats enable parallel transformation of assembled constructs 5 .
Scientists synthesize genes with specific mutations to study their functions 3 .
Research exploring how to encode digital information in synthetic DNA sequences 9 .
Companies offer high-throughput DNA library assembly services for optimizing chemical production 8 .
Ensuring the responsible use of synthetic biology capabilities requires ongoing attention and appropriate governance frameworks.
Synthesizing extremely long, complex sequences—particularly those with high repetition or unusual structural features—continues to push boundaries.
Closing the gap between our ability to read DNA (which remains more advanced) and write it remains an active area of innovation 7 .
As synthesis technologies advance, the focus is shifting from technical feasibility to responsible application for global challenges.
High-throughput DNA synthesis has transformed biology from a predominantly observational science to a design-oriented discipline. What was once the exclusive domain of nature can now be engineered, optimized, and created from scratch in laboratories worldwide.
As synthesis technologies continue to advance in speed, accuracy, and accessibility, they empower scientists to address fundamental biological questions and develop solutions to global challenges in healthcare, sustainability, and beyond.
The progression from first-generation chemical synthesizers to modern enzymatic platforms represents more than just technical improvement—it signifies a fundamental shift in our relationship with the code of life. We are moving from being readers of genetic information to becoming its writers, with all the accompanying opportunities and responsibilities.
As this field continues to evolve, the question is shifting from "Can we synthesize this DNA?" to "What DNA should we synthesize to create a better world?" 6