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Enzymatic Synthesis Technology for Nucleic Acid Drugs

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Nucleic acid drug enzyme synthesis technology achieves customized nucleic acid drugs through the use of specific nucleases for the precise cleavage, synthesis, and modification of DNA/RNA molecules. CD Formulation offers an advanced enzyme synthesis methodology platform to assist customers in developing and producing a wide range of nucleic acid drugs more efficiently, thereby promoting the advancement of precision medicine.

Advantages of Enzymatic Synthesis Technology for Nucleic Acid Drugs

Nucleic acid drugs are prepared through enzymatic cleavage of the target sequence by nuclease action. The major advantage of this method is its suitability for large-scale reaction systems with a rapid reaction rate. Additionally, it enables the preparation of nucleic acid drugs with specific sequences, lengths, and modifications.

Fig.1 Enzyme synthesis technology advantages for nucleic acid drugs Fig.1 Advantages of nucleic acid drug synthesis. (CD Formulation)

Enzymes for Nucleic Acid Drug Synthesis Technology

CD Formulation's nucleases enable customers to conduct nucleic acid operations such as shearing, splicing, synthesis, and modification efficiently, thereby advancing nucleic acid drug development and production. Here are some common types of nucleases along with their features and advantages.

Enzymes	Characteristics	Advantages
Restriction Endonucleases	Capable of recognizing and specifically cleaving particular sequences in DNA double strands (typically recognition sequences 4-8 base pairs long). Forms sticky or blunt ends after cleavage.	High specificity allows for very precise shearing of DNA, facilitating the ligation and cloning of specific fragments.
DNA Polymerases	Extend from the 3'-OH end under the guidance of the template strand for DNA synthesis in the presence of a sufficient supply of nucleotides. This process involves various enzymes such as Taq DNA polymerase, Pfu DNA polymerase, Klenow fragments, etc.	High-fidelity DNA polymerases (some specific types such as Pfu) are widely used in PCR amplification due to their high efficiency.
RNA Polymerases	Synthesize RNA from a DNA template using enzymes like T7 RNA polymerase and SP6 RNA polymerase.	High speed and specificity make it especially effective in in vitro transcription reactions.
DNA Ligases	Capable of joining phosphodiester bonds between the 5' phosphate and 3' hydroxyl groups of DNA fragments.	Highly efficient in ligating DNA fragments, contributing to DNA recombination and cloning.
Reverse Transcriptase	Synthesizing cDNA (complementary DNA) using RNA as a template is a common practice, often employing enzymes like M-MLV and AMV reverse transcriptase.	They can effectively reverse transcribe RNA into DNA, which is especially crucial for studying gene expression and constructing expression libraries.

Capabilities of Enzyme Synthesis Technology for Nucleic Acid Drugs Preparation

CD Formulation's dedicated team and state-of-the-art laboratory equipment ensure a high degree of customization of nucleic acid drugs in terms of specific sequences, lengths, and modifications to meet the diverse R&D needs of our customers. This enables efficient, rapid, and reliable production in large-scale reaction systems. With our advanced enzyme synthesis technology and extensive experience, we possess the following capabilities.

Length Customization of Nucleic Acid Drugs

Our enzyme synthesis technology is fully capable of meeting your DNA sequence lengths of 10,000 bases or more. This ultra-long DNA synthesis capability will provide templates long enough for your CRISPR insertion experiments, ensuring that the length of your DNA tools does not limit your experiments.

Purity Control of Nucleic Acid Drug

In contrast to chemical synthesis, we are able to produce error-free DNA/RNA sequences using an enzymatic synthesis process optimized for natural evolution. The purity of DNA/RNA synthesized by this biological process can reach over 99.99%.

Scale-up of Nucleic Acid Drugs

With our advanced enzymatic synthesis technology and complete production line, we are able to rapidly scale up the production of DNA sequences according to the needs of our customers. Whether you need a small amount of customized sequences or large quantities of DNA for industrial use, we have the flexibility to respond.

Highlights of Nucleic Acid Drug Enzyme Synthesis Technology

We have various types of enzymes to customize a wide range of nucleic acid drugs, such as ASOs, mRNAs, etc., and provide options for different lengths.
Our nucleic acid drugs can be purified and tested using our professional technology platform to ensure they meet the customized needs of our customers in the medical industry.
Our technology platform is flexible and comprehensive to meet customer requirements for all stages of our process, including nucleic acid design, validation, preparation, testing, and production.

Custom Nucleic Acid Drug Development Services

CD Formulation offers enzymatic customization services to customize small nucleic acid drugs and mRNA drugs using advanced enzymatic synthesis and modification technologies.

Custom Small Nucleic Acid Synthesis

Our technology enables the preparation of small nucleic acid drugs by precisely synthesizing specific nucleic acid sequences in an in vitro system, utilizing highly specific enzymes such as polymerases and nucleic acid endonucleases.

Custom mRNA Synthesis

Our enzyme technology platform employs highly efficient in vitro transcription techniques to customize mRNA synthesis. We utilize specially designed DNA templates and high-purity RNA polymerases to ensure both the efficiency and accuracy of the synthesis process.

Publication Data

Technology: Synthesizing DNA by enzyme technology

Journal: Proceedings of the National Academy of Sciences

IF: 9.4

Published: 2007

Results:

Glycerol nucleic acid (GNA) is an interesting alternative base-pairing system based on a non-cyclic glycerophosphate backbone repeating unit. Since GNA is unable to form stable double strands with DNA, the ability of DNA polymerases to catalyze efficient template-dependent synthesis using GNA as a template is a matter of particular interest. In this study, the authors screened a variety of DNA polymerases for GNA-dependent DNA synthesis. The authors found that Bst DNA polymerase can catalyze full-length DNA synthesis on a dodecameric GNA template. Substitution of adenine for diaminopurine in the GNA template and DNA monomers and the presence of manganese ions increased the efficiency of DNA synthesis. The authors concluded that BstDNA polymerase maintains a transient base-pairing region between the DNA product strand and the GNA template, but that template-dependent polymerization does not require the formation of a stable double strand between the product and template strands.

Fig.2 Enzymatic synthesis of DNA on glycerol nucleic acid templates Fig.2 Time-dependent synthesis of DNA on a GNA template catalyzed by Bst polymerase. (Tsai C H, et al., 2021)

With flexible and customized manufacturing capabilities, scale-up advantages, and responsive delivery, CD Formulation is confident that we can be your ideal supplier of nucleic acid drugs. Our specialized technology platform enables us to conduct rigorous purification and quality testing to ensure that our products meet the stringent standards of the medical industry. Contact us for our ability to customize a formulation solution for you.

References

Tsai C H, Chen J, Szostak J W. Enzymatic synthesis of DNA on glycerol nucleic acid templates without stable duplex formation between product and template. PNAS. 2007, 104(37): 14598-14603.

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