Various modifications are applied to small nucleic acids to enhance their stability, reduce immunogenicity, and improve targeting. Below are the most commonly used modifications and their primary functions:
● Phosphorothioate (PS) Modification: Substitution of one of the non-bridging oxygen atoms in the phosphodiester backbone with sulfur.
● Main Function: Increases stability by protecting against nuclease degradation.
● 2'-O-Methyl (2'-OMe) Modification: Addition of a methyl group at the 2' position of the ribose sugar.
● Main Function: Enhances resistance to nuclease activity and reduces immune activation.
● Locked Nucleic Acid (LNA): Modification of the ribose sugar to "lock" the sugar in a particular conformation.
● Main Function: Improves hybridization affinity and stability, especially for ASOs and miRNAs.
● Fluorescent Labels: Attachment of fluorescent molecules to the oligonucleotide.
● Main Function: Used for tracking, imaging, and studying the distribution of nucleic acids.
● Cholesterol Conjugation: Adding a cholesterol group to the oligonucleotide.
● Main Function: Enhances cellular uptake and promotes delivery across cell membranes.
● Polyethylene Glycol (PEG) Conjugation: Attachment of PEG chains to the nucleic acid.
● Main Function: Increases solubility, reduces immunogenicity, and prolongs circulation time in vivo.
These modifications are strategically used to optimize the pharmacokinetics, stability, and therapeutic efficacy of small nucleic acids.
GenCefe Biotech provides high-quality siRNA, miRNA, sgRNA, and custom RNA synthesis services. We can design and synthesize RNA Oligos of different lengths, different forms, and with various modifications according to customer’s needs, and also synthesize RNA sequences designed by customers. The RNA products we deliver are all purified by HPLC. ISO 9001-certified facilities and comprehensive quality control reports ensure the delivery of high-quality products.
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