CD Formulation offers a comprehensive suite of nucleic acid modification services that empower researchers and innovators across various industries to explore new frontiers. From custom nucleic acid synthesis to advanced chemical modifications, we provide a diverse array of capabilities to address the distinct requirements of our clients. Our team of specialists collaborates closely with you to devise and execute customized solutions aimed at enhancing the structure, functionality, and efficacy of your nucleic acid products and applications.
Nucleic acid modification refers to various alterations on DNA and RNA bases (A, T, G, C, U) as well as ribose, and is a crucial aspect of epigenetic regulation. It is a branch of genetics that involves heritable changes in gene expression without changing the nucleotide sequence of genes, thereby regulating various physiological functions. The normal growth and development of the human body are closely linked to the accurate maintenance of DNA methylation levels. Abnormal methylation levels can result in the abnormal expression of relevant genes, leading to the development of diseases. Nucleic acid modification has been associated with a wide range of diseases, including metabolic diseases, neurological disorders, psychiatric disorders, cardiovascular diseases, endocrine system disorders, tumors, inflammation, and immunity.
Fig.1 Application of nucleic acid modification. (CD Formulation)
CD Formulation, as a professional nucleic acid modification service provider, is capable of delivering customized and high-quality modified nucleic acid products through its advanced technology platform and extensive experience. Currently, we can provide you with many types of nucleic acid modification services as listed below.
Items | Descriptions | Advantages |
---|---|---|
Phosphate Modification | Phosphate group modification is often performed on unbridged oxygen atoms. The most common method involves substituting sulfur atoms for one of the unbridged oxygen atoms of the phosphate group, creating a phosphorothioate bond. | It can greatly enhance the stability, membrane permeability, and targeting of nucleic acid molecules, thereby significantly improving their bioavailability and therapeutic effects. |
Base Modification | The modification of bases mainly involves the substitution or replacement of bases, with the 5-position of pyrimidine and the 8-position of purine being common substitution sites. | Significantly improve the chemical and biological stability of nucleic acid molecules, and optimize their binding affinity and selectivity for targets. |
Ribose Modification | There are two main types of ribose modifications. One type involves introducing groups of different sizes and polarities at the 2' position. The other type involves modifying the 2' position and other ribose sites simultaneously. | Enhancing the biological activity, cell penetration, and metabolic stability of nucleic acid molecules can increase their potential for clinical applications. |
Fig.2 Flow chart of nucleic acid modification. (CD Formulation)
Firstly, it is essential to identify the type of nucleic acid modification required based on the specific application requirements. Simultaneously, defining the target site of modification and the anticipated effects, such as enhancing stability, affinity, targeting, etc., is also crucial.
According to the target modification type, chemical synthesis techniques are utilized to design suitable modification reagents and reaction conditions. Typically, the phosphoramidite method and solid-phase synthesis are used to introduce the target modifying groups during nucleic acid synthesis.
After the synthesis is completed, high-performance liquid chromatography (HPLC) and mass spectrometry (MS) are used to purify and identify the modified products to ensure their purity, yield, and structure.
The purified modified nucleic acids were tested for various biological properties, such as thermal stability, nuclease resistance, cell transfection efficiency, and target affinity. The test results will be used to evaluate the modification effect and optimize the modification strategy.
Our professional nucleic acid modification service can provide a variety of synthesis technology support, including the following methods.
Chemical Synthesis - Nucleic acids are synthesized using phosphoramidite chemistry on solid or solution phases, and various modifying groups are introduced during the synthesis process.
Enzymatic Synthesis Method - The synthesis of nucleic acids is catalyzed by biological enzymes such as DNA/RNA polymerase, and modified nucleic acid bases or ribose units are introduced during the synthesis process.
Biochemical Modification - A pre-synthesized nucleic acid molecule is chemically or enzymatically modified to introduce a modifying group at a specific site.
CD Formulation has developed an LC-MS/MS platform for the analysis of nucleic acid modifications, providing an ideal technology for epigenetic studies. Liquid chromatography tandem mass spectrometry (LC-MS/MS) can detect compounds with high polarity and poor stability effectively, and can accurately quantify substances. Combining LC-MS/MS with specific sample pre-treatment methods enables improved detection of DNA/RNA modifications in various biological samples.
Technology: DNA/RNA modification by base modification technology
Journal: Computational and structural biotechnology journal
IF: 6
Published: 2020
Results:
The authors summarize the characteristics of DNA and RNA modifications, the available mapping and editing tools, and the potential applications and shortcomings of these techniques in basic and translational research. Various modifications greatly increase the information-encoding capacity of DNA and RNA by introducing additional chemical groups to existing bases rather than altering the gene sequence. As markers on DNA or RNA, nucleic acid modifications can be recognized by specific proteins, enabling versatile regulation of gene expression. Recently, several new techniques have emerged to identify the locations of various modifications on DNA and RNA. Interestingly, by integrating region-targeting tools and effector proteins, researchers are beginning to actively control the modification status of desired genes in vivo.
Fig. 3 Diverse modifications on nucleic acids and their possible functions. (Chen L Q. et al., 2020)
As a leading provider of cutting-edge biotechnology solutions, CD Formulation is committed to supporting researchers in advancing the possibilities of nucleic acid modification. Please feel free to contact us for a convenient overview of our comprehensive services that can assist you with your next project.
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