Therapeutic Nucleic Acid Development Platform

Overview

Therapeutic oligonucleotides, including antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), and therapeutic messenger RNAs (mRNAs), represent a paradigm shift in drug development, enabling the modulation of gene expression with unprecedented specificity. The field has rapidly transitioned from niche research to a powerful modality poised to treat a vast array of diseases, from genetic disorders to chronic conditions. As a class of single- or double-stranded synthetic nucleic acid polymers, oligos function by precisely binding to target RNA or DNA to modulate gene expression, offering an unprecedented level of therapeutic specificity. CD BioGlyco' therapeutic nucleic acid development platform is an integrated, end-to-end solution designed to accelerate your molecule from concept to clinic, tackling the crucial challenges of stability, delivery, and bioavailability with proprietary science and proven expertise.

Core Technologies

• Advanced Solid-Phase Synthesis (SPS)

We employ the highly mature and scalable phosphoramidite chemistry method for the synthesis of oligonucleotides (DNA, RNA, ASOs, siRNA, etc.). Our systems are optimized to maximize coupling efficiency, minimizing the generation of N-1 byproducts and ensuring superior purity, which is critical for therapeutic applications.

• Optimized In Vitro Transcription (IVT)

For mRNA therapeutics, our platform utilizes proprietary protocols for highly efficient IVT. This includes the implementation of clean DNA template preparation, optimized incorporation of modified nucleotides to enhance stability and reduce immunogenicity, and guaranteed high-efficiency capping and poly(A) tailing to mimic native mRNA.

• Precision Conjugation Chemistry (e.g., GalNAc)

For targeted delivery, especially to the liver, we specialize in the synthesis of complex conjugate molecules. Our expertise spans solution and solid-phase synthesis for producing high-purity GalNAc ligands, including mono-, bi-, tri-, and tetra-antennary designs, enabling superior hepatocyte targeting efficiency for ASOs and siRNAs.

• Lipid Nanoparticle (LNP) Formulation

LNPs remain the gold standard for systemic delivery, particularly for mRNA vaccines and therapeutics. Our platform includes scalable, controllable microfluidic mixing and robust downstream processing for the efficient encapsulation of nucleic acids, ensuring optimal particle size, polydispersity, zeta potential, and encapsulation efficiency necessary for clinical use.

Integrated Oligonucleotide Development: From Sequence to Success.

We commence our integrated oligonucleotide development pipeline with computationally-guided sequence design and wet-lab screening, incorporating mRNA optimization, off-target assessment, and strategic modifications (PS, 2'-OMe, PNA, novel nucleosides) to bolster stability, potency, and reduce immunogenicity. We then advance to scalable, automated synthesis on high-fidelity platforms, executing custom conjugations (GalNAc, PEG, peptides) and precise modification integration. Our team subsequently applies advanced purification via HPLC and TFF to achieve exceptional purity, complemented by rigorous QC using mass spectrometry, gel electrophoresis, and UPLC for verifying sequence, purity, integrity, and yield. We then engineer tailored delivery systems, including mRNA-LNP encapsulation and stable drug product development for naked/conjugated oligonucleotides, covering parenteral and lyophilized formulations. Our process culminates in comprehensive biological evaluation and CMC support, encompassing ADME profiling, potency assays, mRNA bioanalysis (biodistribution), and establishing robust, scalable production/purification processes.

• Therapeutic Oligonucleotide Delivery Development Service

Recognizing that effective delivery is the single most critical factor for clinical success, we offer a comprehensive delivery platform dedicated to optimizing the stability and tissue-specific uptake of oligonucleotide therapeutics. A cornerstone of this platform is our GalNAc Ligand Design & Synthesis Service, which involves the custom design and production of GalNAc ligands with varying valencies to achieve optimal asialoglycoprotein receptor (ASGPR)-mediated liver targeting.

• By GalNAc Type

• By Chemical Reaction

• By Oligonucleotide Type

• Other Delivery Technologies

• Biological Evaluation Service for Therapeutic Oligonucleotide

• mRNA-based Vaccine Development Service

We offer end-to-end solutions for mRNA-based vaccines, from design through purification and delivery, leveraging the unprecedented speed and flexibility of this modality.

• Oligonucleotide Drug Process and Formulation Development Service
  Our focus is on engineering scientifically sound, robust, and scalable processes that de-risk your program through late-stage clinical trials.
  • RNA Production and Purification Process Development Service: Optimization of solid-phase synthesis and downstream purification (e.g., Ion-Exchange Chromatography) to define high-yield, high-purity, and scalable processes.
  • RNA Drug Formulation Development Service: Development of stable and bioavailable drug product formulations.
    • Oral Solid Dose Formulation Development Service
    • Rectal Dosage Formulation Development Service
    • Non-sterile Liquid Dose Formulation Development Service

    • Sterile Liquid Formulation Development Service
    • Lyophilized Drug Formulation Development Service

  Workflow

  

  Publication Data

  Journal: Signal transduction and targeted therapy

  DOI.: 10.1038/s41392-024-02035-4

  Published: 2024

  Results: This comprehensive review article delves into the recent progress and future perspectives of nucleic acid drugs, a promising class of therapeutics including ASOs, siRNAs, mRNAs, and gene-editing tools like CRISPR/Cas9. The authors systematically detail the mechanisms of action, such as gene silencing and protein replacement, and address significant challenges in nucleic acid drug development, particularly concerning stability, targeted delivery, and immunogenicity. They explore innovative strategies to overcome these hurdles, emphasizing chemical modifications and advanced delivery systems like lipid nanoparticles and viral vectors. The review highlights the successful clinical translation of various nucleic acid drugs for treating a range of diseases, from rare genetic disorders and cancers to infectious diseases, showcasing notable examples like mRNA vaccines for COVID-19. Finally, the authors discuss ongoing challenges and future directions, underscoring the potential of nucleic acid drugs to revolutionize personalized medicine while pointing to the need for improved delivery efficiency and long-term safety profiles.

  Applications

  • Research on Novel Nucleic Acid Architectures

  Our service prioritizes the elaboration and scrutiny of sophisticated nucleic acid architectures, encompassing circular RNA, self-amplifying RNA, and nucleic acid scaffolds, to probe their efficacy in fortifying stability, extending expression duration, and amplifying functional complexity for diverse applications.

  • Development of Targeted Delivery Systems

  Our platform is applied to engineer and optimize non-viral delivery vectors, such as lipid nanoparticles (LNPs) and polymeric nanoparticles, for the specific purpose of achieving efficient and cell-selective nucleic acid delivery in research models.

  • Exploration of Gene Modulation Mechanisms

  We utilize this platform to develop tools for studying gene function regulation, including the use of siRNA for knock-down studies, mRNA for transient overexpression, and CRISPR-based components for gene editing research.

  • Engineering of Cell-Based Therapeutic Models

  This platform supports the development of ex vivo strategies, where cells are engineered with nucleic acids to express therapeutic proteins or chimeric antigen receptors (CARs) for subsequent research in adoptive cell therapies.

  • Development of Diagnostic and Sensor Tools

  We apply nucleic acid technology to build in vitro and in vivo biosensors and diagnostic reporters, facilitating the study of biological pathways and disease biomarkers.

  • Investigation of Immunomodulatory Pathways

  Our work involves designing immunostimulatory or immunosuppressive nucleic acids to study and manipulate immune cell functions, vaccine responses, and autoimmune reactions in a controlled research environment.

  Advantages

  • Integrated, Single-Source Expertise

  Unlike fragmented providers, we offer a truly holistic solution, managing everything from de novo sequence design to final dosage formulation. This eliminates complex tech transfers, significantly reducing project timelines and mitigating critical development risk. Our deep expertise in both solid-phase oligo synthesis and IVT-based mRNA production ensures a cohesive strategy, regardless of your modality.

  • Unmatched Purity and Scalability

  Our rigorous purification protocols consistently yield therapeutic-grade nucleic acids with >95% purity, often exceeding industry benchmarks. We have successfully manufactured complex, highly-modified oligonucleotides and long-chain mRNAs.

  • Targeted Delivery System Innovation

  Our dedicated delivery chemistry team is a leader in GalNAc conjugate design, including complex multi-antennary structures, optimizing target engagement with the asialoglycoprotein receptor (ASGPR) for liver therapeutics. Similarly, our LNP formulation expertise ensures high encapsulation efficiency and the ideal physicochemical profile (size, PDI) for optimal performance in vivo.

  • Robust CMC and Regulatory Readiness

  We build quality into every step. Our process development is executed with a clear path, utilizing control strategies that align with global regulatory expectations. The mRNA structural characterization service is particularly comprehensive, providing assurance of critical quality attributes like Cap integrity and dsRNA minimization.

  Frequently Asked Questions

  Customer Review

  • "The off-target activity assessment service was instrumental in de-risking our lead candidate. Their data was rigorous, comprehensive, and stood up flawlessly during our internal safety review."

  — Dr. Peterson, Senior Director, Molecular R&D

  • "The speed of the integrated service—from design to encapsulated LNP—was truly impressive. They hit our aggressive timeline for the IND-enabling studies. Their responsiveness and expertise in LNP customization were key to our program's success."

  — Manager Chen, Program Director, Infectious Disease Therapeutics

  • "The custom conjugate potency assay they designed for our lipid-oligonucleotide platform was perfect. They accurately confirmed the cellular internalization efficiency and functional knockdown, validating our delivery strategy with confidence."

  — Research Director, Bioanalysis

  Associated Services

  Our therapeutic nucleic acid development platform establishes innovative approaches for nucleic acid-based therapeutics, while our parallel Carbohydrate-based Glycomedicine Development Platform advances novel biologic development through Oligosaccharide and Polysaccharide engineering for targeted therapeutic applications.

  CD BioGlyco stands as your dedicated, expert partner in the rapidly evolving landscape of genetic medicine. Our therapeutic nucleic acid development platform combines scientific expertise, state-of-the-art technology, and a commitment to unparalleled product quality and customer partnership. If you want to translate your nucleic acid therapeutic from a potent sequence into a viable, market-ready drug candidate, contact us.

  Reference

  1. Sun, X.; et al. Nucleic acid drugs: recent progress and future perspectives. Signal transduction and targeted therapy. 2024, 9(1): 316. (Open Access)
  This service is for Research Use Only, not intended for any clinical use.