Design, Optimization and Coupling Process Development of Antisense Oligonucleotide
Antisense oligonucleotides (ASODN) usually refer to short nucleic acids consisting of 15 to 25 nucleotides that have undergone some chemical modification. An important characteristic of ASODN is the high sequence specificity of its target RNA. The high fidelity of its sequence is that ASODN can regulate a single member gene of a gene family, and even a certain variant of a member gene. This is something that other technique at the protein level can’t do. ASODN is widely used in drug target screening and drug design. ASODN technology including: 1. Chemical modification of ASODN; 2. Design and screening of ASODN; 3. Study on the mechanism of ASODN; 4. Construction and application of technology platform; 5. Determination of gene function and selection of drug targets.
Creative Biolabs is the world's leading supplier of ASODN customized productions and services. Creative Biolabs has leading ASODN synthesis, purification and analysis platform. Professional personnel in Creative Biolabs provide quality and reliable ASODN products, and build a manufacturing workshop in line with international standards which meet the small scale, pilot to large-scale commercial production. Creative Biolabs has been providing high-quality ASODN synthesis and customized service to global partners for many years.
Categories of Chemical Modifications:
- First-generation ASODN. Phosphodiester bond is the backbone of nucleic acid chain, in which the P-O bond can be hydrolyzed by nuclease, resulting in oligonucleotide depolymerization. Modification of phosphodiester bond is an important mean to improve its resistance to nuclease. According to the principle that S and O are congeners, Creative Biolabs replace non-bridging oxygen atoms on the antisense oligonucleotide skeleton with sulfur atoms, forming the P-S bond which is most similar to the natural phosphodiester bond. The substituted product is phosporothioate deoxyoligleotide (PS-ODN), which is the first-generation ASODN.
- Second-generation ASODN. Creative Biolabs can help customers further improve the properties of ASODN, overcoming the limitations of first-generation ASODN, resulting in designing second-generation chimeric ASODN. On the basis of PS-ODN, Creative Biolabs modifies the 2' positions on the two wings or the middle ribose of the sequence with other groups, such as 2' -methoxyethyl. As it contains most kinds of skeleton forms, it is called methoxyethy (MBO).
- Third-generation ASODN. Creative Biolabs replaces phosphodiester bond skeletons in DNA molecules with the repetitive N- (2-aminoethyl) glycine units connected by amide bonds to form an analog of a DNA molecule which is peptide nucleic acid (PNA). The purines and pyrimidines of PNA are attached to the nitrogen atoms of glycine by methylene carbon.
Advantages of ASODN service:
- Professional technical team: more than 10 years of ASODN production experience, successfully delivered over one million pieces of nucleic acid.
- Leading modification and customization capabilities: provide richer modifier types and flexible customization services.
- Strict quality control management: international standard workshop, in line with ISO and ICHQ7a requirements.
- Advanced equipment and instruments: the introduction of the world's leading nucleic acid synthesis, purification and analysis instruments.
- Perfect project management: Standardize the project management process, and carry out the whole project implementation accurately.
- Meet the requirements of each stage: product types are diverse, providing production services from microgram to kilogram level.
References
- Geary RS, et al. Pharmacokinetics, biodistribution and cell uptake of antisense oligonucleotides. Adv Drug Deliv Rev. 2015, 87:46-51.
- Bennett CF. Therapeutic Antisense Oligonucleotides Are Coming of Age. Annu Rev Med. 2019, 70:307-321.
- Crooke ST, et al. Cellular uptake and trafficking of antisense oligonucleotides. Nat Biotechnol. 2017, 35(3):230-237.
*For Research Use Only. Not for use in diagnostic procedures.