Cell & Developmental Biology
Open Access

Advancements in Artificial Gene Synthesis Technologies: Overcoming Challenges in DNA Production

Daniel Xeira^{* *}Correspondence: Daniel Xeira, Department of Cell Biology, King’s College London, London, United Kingdom, Email:

Author info »

Description

Artificial gene synthesis has transformed the landscape of molecular biology, enabling the creation of custom Deoxyribonucleic Acid (DNA) sequences for a wide array of applications, from basic research to therapeutic development. As the demand for synthetic DNA continues to grow, advancements in gene synthesis technologies are important for overcoming the challenges associated with DNA production, particularly in terms of cost, scalability, and accuracy. This article explores recent innovations in artificial gene synthesis technologies and their implications for various fields.

Basics of artificial gene synthesis

Artificial gene synthesis refers to the de novo construction of genes from nucleotides, allowing researchers to create specific DNA sequences without relying on natural templates. The process typically involves two main steps, those are

Solid-phase DNA synthesis: This step produces short oligonucleotide fragments, generally less than 200 base pairs in length, using methods such as phosphoramidite chemistry.

Assembly of oligonucleotides: The short fragments are then connected through various assembly methods, such as Polymerase Cycling Assembly (PCA) or ligation techniques, to form longer DNA sequences or entire genes.

Historically, the synthesis of longer DNA sequences causes significant challenges due to limitations in the length of oligonucleotides that could be reliably produced. However, recent advancements have addressed these challenges, enabling the synthesis of larger and more complex DNA constructs.

Overcoming challenges in DNA production

Improved synthesis techniques: One of the primary challenges in artificial gene synthesis has been the production of long DNA sequences. Traditional solid-phase synthesis methods are limited to short oligonucleotides, necessitating the development of innovative techniques to assemble longer sequences. Recent advancements include:

Polymerase Cycling Assembly (PCA): PCA allows for the efficient assembly of longer DNA fragments by using overlapping regions between oligonucleotides. This method has become the dominant approach for synthesizing larger genes and genomes, significantly reducing the time and cost associated with gene synthesis.

Microarray-based synthesis: Companies like Twist Bioscience have pioneered microarray technology, which enables the synthesis of thousands of oligonucleotides in parallel on a silicon chip. This method not only increases throughput but also reduces costs by allowing high-density synthesis of multiple sequences simultaneously.

Template-independent enzymatic synthesis: This emerging technique allows for the synthesis of DNA without the need for a template strand, further expanding the possibilities for creating novel sequences.

Error correction and fidelity enhancement: The accuracy of synthesized DNA is difficult for its functionality in biological applications. Advances in error correction methods have been developed to enhance the fidelity of gene synthesis are:

High-fidelity polymerases: The use of high-fidelity DNA polymerases during assembly processes helps minimize errors in the final product.

Error correction protocols: Techniques such as Next-Generation Sequencing (NGS) can be employed to identify and correct errors in synthesized DNA, ensuring the integrity of the final construct.

Cost reduction strategies: As the demand for synthetic DNA grows, the need for cost-effective solutions becomes paramount. Several strategies have emerged to reduce the costs associated with gene synthesis are:

Automation: The automation of DNA synthesis processes reduces labor costs and increases throughput. Companies are developing benchtop DNA synthesizers that can produce oligonucleotides rapidly and at lower costs.

Economies of scale: As more companies enter the synthetic DNA market, competition drives prices down. Additionally, large-scale production methods allow for significant cost savings, making synthetic DNA more accessible to researchers and companies alike.

Implications for research and industry

Synthetic biology: The ability to create custom genes facilitates the design of synthetic organisms, enabling researchers to explore biological functions and interactions in unprecedented ways. This capability is essential for developing synthetic biological systems, such as engineered microbes for bioremediation or biofuel production.

Gene therapy: Artificial gene synthesis plays a crucial role in the development of gene therapies, where synthetic genes can be designed to replace defective genes or introduce new functions into cells. The ability to produce high-quality, custom DNA sequences is vital for the success of these therapies.

Vaccine development: The rapid synthesis of synthetic DNA has been instrumental in the development of DNA vaccines, which provides a path to immunization against infectious diseases. The ability to quickly design and produce vaccine candidates in response to emerging pathogens is critical for public health.

Conclusion

Advancements in artificial gene synthesis technologies are overcoming the challenges associated with DNA production, paving the way for innovative applications in synthetic biology, gene therapy, and vaccine development. By improving synthesis techniques, enhancing fidelity, and reducing costs, researchers can now produce high-quality synthetic DNA more efficiently than ever before. As these technologies continue to evolve, they hold the potential to revolutionize our understanding of biology and expand the possibilities for therapeutic interventions, ultimately leading to significant advancements in medicine and biotechnology.