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Antisense Oligonucleotide Therapy Development

Single-gene inherited gene deletions, insertions, and mutations lead to most rare diseases. Antisense oligonucleotide (ASO) therapy is one of the effective platforms for developing drugs for rare diseases. Our company is focused on improving ASO-based sequences and chemical modifications and helping our customers develop ASO-based gene therapies to achieve breakthroughs in the treatment of rare diseases.

Background

Oligonucleotide therapies serve to up- or down-regulate gene expression by introducing short-chain nucleotides (DNA or RNA) within 20 without interfering with the gene itself. There are many types of oligonucleotide drugs currently under research, including ASO, siRNA, microRNA, aptamer, etc. ASOs are defined as chemically synthesized oligonucleotides that can sequence-specifically bind pre-mRNA or mRNA. They can post-transcriptionally regulate protein synthesis through mechanisms such as steric blockade of the translational machinery, competitive inhibition, and modification of pre-mRNA processing and splicing.

ASO drugs are widely used in the treatment of rare diseases because of their high specificity and low adverse effects. In addition to several approved drugs, such as eteplirsen and golodirsen, which are ASOs for the treatment of Duchenne muscular dystrophy (DMD), there are many ongoing clinical trials using ASOs. Preliminary data from these trials suggest that ASO-based therapies may provide a rich source of new treatments for rare diseases that were previously difficult to treat.

Fig. 1 Examples of ASO-based RNA drugs.

Fig. 1 Examples of ASO-based RNA drugs. (Kim Y K, 2022)

Our Services

Our extensive expertise and experience in rare disease genome sequencing and oligonucleotide rational design allow us to provide our customers with reliable scientific services to accelerate the development of projects related to rare disease ASO-based therapies. Our advanced chemical synthesis technology and the full spectrum of analytical tools help you develop safe and effective drug candidates. We ultimately provide you with customized products and all the raw data, normalized data, and the final output as a scientific report.

  • ASO Synthesis
    Our company offers our customers the synthesis of sequence-specific ASOs using DNA, 2'-O-methoxyethyl RNA, 2'-O-methyl RNA, or restricted nucleotide bases with phosphorothioate or unmodified inter-nucleotide bonds. Moreover, we purify and characterize the synthesized ASOs using various techniques such as high-performance liquid chromatography (HPLC).
  • ASO Modification
    We offer chemical modifications of ASO nucleobases, nucleosides, and inter-nucleoside backbones to improve the pharmacokinetics and pharmacodynamics of ASO-based drugs while maintaining target affinity. We usually improve the stability and RNA binding affinity of ASOs through 2' ribose modifications that include 2'-O-methoxy-ethyl (MOE), 2'-O-methoxy (OMe), and locked nucleic acid (LNA).
  • Improvement of ASO delivery to the target sites
    We covalently bind oligonucleotide loads to carriers or ligands, such as liposomes, lipid particles, nanoparticles, and sugar N-acetylgalactosamine, to enhance safe delivery to target sites.

In conclusion, we offer our customers multiple chemical modifications and designs for ASO therapeutics aimed at:

  • Enhancing binding affinity to target RNA
  • Increasing metabolic stability
  • Reducing adverse effects and phosphate modifications
  • Increasing protein binding for the improvement of tissue distribution and cellular uptake

Our company is a biotechnology company focused on the development of novel, breakthrough ASO-based gene therapies for rare diseases. We utilize innovative synthetic and manufacturing technologies along with superior scientific services to meet our customers' needs for gene therapy development for rare diseases. If you are interested in our services, please contact us for more details.

Reference

  • Kim, Y. K. RNA therapy: rich history, various applications and unlimited future prospects. Experimental & Molecular Medicine, 2022, 54(4): 455-465.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.

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