In recent years, small nucleic acid drugs have become a hot affairs of current research in the field of biomedicine due to their advantages of strong specificity, easy design, short development cycle, and rich targets; small nucleic acid drugs specifically refer to a class of oligonucleotide molecules targeting RNA or proteins, including antisense oligonucleotides (ASOs), siRNAs, and aptamers, etc.; antisense oligonucleotides (ASOs) are usually made up of 15-25 nucleotides, and some chemical modification of the short chain nucleic acid, its bases through the (watson-crick) base complementary pairing principle and the target to form a double-stranded structure.

ASO Drugs VS Small Nucleic Acid Drugs

Mechanism of Action
ASOs are single-stranded oligonucleotides that bind to target mRNA or pre-mRNA by the principle of base complementary pairing to form a DNA/RNA double-stranded structure. This binding can inhibit gene function, including inducing RNase H to cleave the RNA strand, thus preventing the synthesis of target proteins. In addition, ASOs can regulate the RNA splicing process.

siRNAs are double-stranded RNA molecules that mainly silence the expression of specific genes through the RNA interference pathway.

Other small nucleic acid drugs, such as miRNAs and saRNAs, also exert their effects on mRNA translation or stability through comparable mechanisms. However, they may differ in their specific modes of action and target sites. In contrast, nucleic acid aptamers harness their unique three-dimensional structures to bind with target proteins and thereby regulate their function.

Chemical Modification 

ASOs for splicing conversion applications consist entirely of chemically modified nucleic acid analogs rather than natural RNA oligomers. This chemical modification significantly improves the efficacy, stability and safety of ASOs as drugs.

siRNA' structure has high molecular weight and is hydrophilic. The weak binding ability to plasma proteins results in a faster clearance rate, making the need for a suitable delivery system and chemical modification even more important.

Target Range

Beyond directly inhibiting protein-coding genes, ASOs also have the capacity to modulate the function of non-coding RNAs, offering a broader spectrum of therapeutic targets. Consequently, ASOs can be utilized in the treatment of various neurological and neuromuscular disorders, such as spinal muscular atrophy and Huntington's disease.

Delivery Systems

ASOs can be administered as naked nucleic acids and are relatively less dependent on delivery systems. However, in order to improve their bioavailability and therapeutic efficacy, there is still a need to develop effective delivery systems.

siRNAs require more complex delivery systems to ensure their effective entry into the cell and function. Commonly used delivery systems include liposomes, polymers, etc.

Other small nucleic acid drugs’ delivery systems also vary depending on their chemical structure and properties. For example, nucleic acid aptamers may require specific ligand binding for targeted delivery.

What’s the Applications of ASO Drugs and siRNA Drugs?

ASOs, a class of small nucleic acid drugs with a long research history and several marketed products, demonstrate significant potential in treating genetic, rare, and refractory diseases. siRNA drugs, another hotspot in current small nucleic acid drug research, have several candidates targeting genetic diseases and cancer that have entered clinical trials or been approved for marketing. Additionally, other small nucleic acid drugs, including miRNAs, saRNAs, and other categories, are under active research and development, with expectations of playing a crucial role in the treatment of even more diseases in the future.

ASOs Drugs & siRNA Drugs

Synbio Technologies |Antisense Oligonucleotides Synthesis

Synbio Technologies offers antisense oligonucleotides (ASOs) that are specifically designed to target complementary RNA and prevent its translation into proteins. Our antisense oligos are able to recognize specific mRNA sequences, thus blocking the translation of corresponding proteins, ultimately leading to the inhibition of gene expression.

ASO Synthesis Services Detail

siRNA Synthesis Services Detail

Reference

1.Bao T. Le, Suxiang Chen, Rakesh N. Veedu. "Evaluation of Chemically Modified Nucleic Acid Analogues for Splice Switching Application." ACS Omega, 2023, 8(51): 48650-48661.

2.Roger M. Lane, C. Frank Bennett. "Antisense oligonucleotide drugs for neurological and neuromuscular disease." (Book chapter), 2020, pp. 221-245.