CpG Oligonucleotide Development

CpG Oligonucleotide Development

CpG oligonucleotides are short single-stranded oligodeoxynucleotides containing CpG motifs and are used in the immunomodulatory response to stimulate Toll-like receptor 9 (TLR9). TLR9 is expressed in human plasmacytoid dendritic cells and B cells and triggers an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. At present, CpG oligonucleotides are being tested both as monotherapy and immunotherapeutic adjuvants in combination with chemotherapy, radiotherapy, and targeted therapy.

Alfa Chemistry focuses on the development of CpG oligonucleotides, committed to maximizing the value of CpG oligonucleotides for the prevention or treatment of diseases such as cancer, allergies and infectious diseases.

Types of CpG Oligonucleotides

There are four categories of CpG oligonucleotides that have been identified: K-type CpG oligonucleotides, D-type CpG oligonucleotides, C-type CpG oligonucleotides, and P-type CpG oligonucleotides[1]. Although each class contains at least one "CpG motif", they differ in terms of structure and immune activity.

K-type CpG oligonucleotides consist of a phosphorothioate backbone having multiple CpG motifs. They stimulate plasmacytoid dendritic cell (pDC) maturation to trigger B cells for the production of IgM and TNF differentiation.

D-type CpG oligonucleotides comprise a mixed backbone encompassing a phosphodiester nucleotide core and phosphorothioate terminals with a single CpG motif. They stimulate pDC maturation and IFN secretion, as well as APC maturation.

C-type CpG oligonucleotides consist of a phosphorothioate backbone with multiple CpG motifs embedded in a central palindrome that forms either dimers or a stem-loop-like structure. They induce the proliferation and differentiation of B-cells and pDC, as well as IL-6 and IFN production.

P-type CpG oligonucleotides consist of a phosphorothioate backbone with numerous CpG motifs and double palindromes that make a hairpin-like structure rich in 3' ends GC and stimulate pDC, B-cells, and IFN-α secretion.

Mechanism of Action of CpG Oligonucleotides

CpG Oligonucleotides are immunomodulatory synthetic oligonucleotides specifically designed to target TLR9 which plays a role in the recognition of pathogen molecules and the activation of the innate immune response. CpG motifs interact with TLR9 and activate B cells and pDCs, enhance the immune response, lead to the proliferation and differentiation of these cells and cytokine secretion, and the activation of genes involved in inflammatory responses. In response to chemotherapy, TLR9 acts as a tumor sensor by recognizing tumor released DNA, triggering an immune response and activating tumor-specific cytotoxic T lymphocytes (CTLs)[2]. This principle is exploited in the application of synthetic CpG oligonucleotides to enhance TLR9-related immune responses.

Key Factors to Ensure the Quality of CpG Oligonucleotides

The key factors to ensure the quality of CpG oligonucleotides are mainly as follows:

Our Development Process

Alfa Chemistry provides therapeutic CpG oligonucleotide development services, and the following is our main development process. No matter which stage of CpG oligonucleotide development you encounter challenges, we will provide you with timely help.

  • Target selection.
  • Sequence design of CpG oligonucleotides.
  • Synthesis and chemical modification of CpG oligonucleotides.
  • Purification and analysis of CpG oligonucleotides.
  • Delivery system selection or development of CpG oligonucleotides.
  • Nonclinical evaluation of CpG oligonucleotides.
  • Scale-up of CpG oligonucleotides.

References

  1. Thakur, S.; et al. A perspective on oligonucleotide therapy: approaches to patient customization. Frontiers in Pharmacology. 2022, 13: 1006304.
  2. Xiong, H.; et al. Recent advances in oligonucleotide therapeutics in oncology. International Journal of Molecular Sciences. 2021, 22: 3295.

Our products and services are for research use only and cannot be used for any clinical purposes.

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