Peptide-Therapeutic Oligonucleotide Delivery Service
Therapeutic oligonucleotides, including small interfering RNA (siRNA), antisense oligonucleotides (ASOs), and messenger RNA (mRNA), represent a transformative class of drugs capable of modulating gene expression with high precision. However, their utility is significantly limited by their large size, high negative charge, and susceptibility to enzymatic degradation. CD BioGlyco provides a sophisticated peptide-therapeutic oligonucleotide delivery service to overcome these biological barriers. By leveraging cell-penetrating peptides (CPPs) and tissue-specific targeting peptides, we facilitate the efficient intracellular transport and cytosolic release of nucleic acid cargoes.
Key Technologies
- CPP Engineering
We utilize arginine-rich or amphipathic peptides that interact with the negatively charged cell membrane to trigger direct translocation or endocytosis. - Targeting Peptide Discovery
Using phage display and computational modeling, we identify and synthesize homing peptides that specifically bind to cell-surface receptors, allowing for organ-specific delivery and minimized systemic exposure. - Smart Linker Systems
We employ stimuli-responsive linkers that remain stable in systemic circulation but rapidly release the oligonucleotide cargo upon entering the reducing environment of the cytosol or encountering specific intracellular proteases.
Advanced Peptide-Therapeutic Oligonucleotide Delivery Service
Our platform integrates advanced peptide engineering with precise conjugation chemistries to create peptide-oligonucleotide conjugates that exhibit enhanced pharmacokinetics and reduced off-target toxicity. Unlike traditional lipid nanoparticles (LNPs), peptide-based delivery systems offer superior biocompatibility and the ability to be fine-tuned for specific cellular uptake mechanisms, ensuring that your genetic therapeutic reaches its intended destination within the complex biological environment.
As a specialized branch of our therapeutic nucleic acid development platform, the therapeutic oligonucleotide delivery service at CD BioGlyco provides end-to-end solutions for the delivery of diverse nucleic acid species. We focus on the design, synthesis, and validation of peptide-based carriers tailored to the unique physicochemical properties of your therapeutic cargo.
- Peptide-oligonucleotide Conjugates Development: Ideal for charge-neutral analogs like phosphorodiamidate morpholino oligomers (PMOs) or peptide nucleic acids (PNAs), utilizing stable or reversible chemical bonds.
- Non-Covalent Complexation: Utilizing cationic or amphipathic peptides to form stable nano-complexes with siRNA or mRNA through electrostatic interactions, protecting them from nuclease degradation.
- Multifunctional Peptide Assembly: Developing complex delivery systems that combine a targeting ligand, a CPP for penetration, and a polyethylene glycol (PEG) spacer to enhance solubility and half-life.
Workflow
Tailored Peptide Design and Optimization
Our experts design custom peptide sequences based on the target cell type and delivery requirements. This includes selecting the optimal amino acid composition, incorporating D-amino acids for metabolic stability, or utilizing cyclization to enhance binding affinity.
Oligonucleotide Chemical Modification
We introduce reactive functional groups (e.g., azides, alkynes, thiols, or amines) at the 3' or 5' terminus of the oligonucleotide. This step also includes backbone modifications such as phosphorothioate (PS) to further resist enzymatic cleavage.
Precision Bioconjugation
Using highly efficient chemistries like Copper-free click chemistry (SPAAC) or thiol-maleimide coupling, we link the peptide to the oligonucleotide. This process is carefully controlled to ensure a defined drug-to-peptide ratio (DPR).
Advanced HPLC Purification
We utilize reversed-phase high-performance liquid chromatography (RP-HPLC) or ion-exchange chromatography (IE-HPLC) to isolate the target peptide-oligonucleotide conjugates from unreacted precursors and byproducts, achieving purity levels typically exceeding 95%.
Stringent Quality Control (QC)
Each batch undergoes a comprehensive analysis. We use electrospray ionization mass spectrometry (ESI-MS) to confirm molecular weight and analytical HPLC to verify homogeneity and stability under physiological conditions.
Biological Functionality Testing
We provide optional in vitro screening, including cellular uptake assays and gene silencing efficiency tests (via RT-qPCR or western blot), to confirm that the delivery system retains its biological activity.
Publication Data
DoI: 10.1089/nat.2014.0511
Journal: Nucleic Acid Therapeutics
IF: 4.7
Published: 2015
Results: This study addresses the poor cellular uptake of charge-neutral splice-switching PMOs by exploring lipid-functionalized cell-penetrating peptides as delivery systems. The researchers tested existing peptides (e.g., PepFect 6, PepFect 14) and novel lipopeptides in cell models of X-linked agammaglobulinemia, spinal muscular atrophy, and Duchenne muscular dystrophy. Results show these lipopeptides form stable nanoparticles with PMOs, efficiently delivering them into hard-to-transfect cells while retaining biological activity (e.g., exon inclusion/skipping). Factors like peptide sequence, lipid chain length, and peptide-PMO ratio influence delivery efficacy, with no significant toxicity at working concentrations. This non-covalent delivery strategy advances PMOs' potential as therapeutics for genetic disorders and research tools.
Fig.1 Nanoparticle tracking analysis (NTA) of PMO formulated by PF6 and PF14. (Järver, et al., 2015)
Applications
Oncology Research
We design conjugates targeting tumor-specific markers to deliver siRNA or ASOs directly to malignant cells, effectively silencing oncogenes while sparing healthy tissues and reducing the systemic side effects of chemotherapy.
Central Nervous System (CNS) Disorders
We help clients enable the delivery of therapeutic oligonucleotides into the brain, providing new avenues for treating neurodegenerative diseases like Alzheimer's and Huntington's through targeted mRNA modulation.
Rare Genetic Disease Therapeutics
By targeting specific muscle or liver receptors, our peptide delivery systems facilitate the uptake of splice-switching oligonucleotides in conditions like Duchenne muscular dystrophy, significantly improving therapeutic bioavailability in distal tissues.
Advantages
Unparalleled Specificity
CD BioGlyco's peptides are engineered to recognize specific cell-surface biomarkers, ensuring that the oligonucleotide cargo is delivered only to the target cells, thereby maximizing efficacy and minimizing off-target risks.
Enhanced Endosomal Escape
Our technology is specifically designed to overcome the "endosomal trap," utilizing pH-responsive mechanisms to ensure the oligonucleotide reaches the cytosol, where it exerts its biological function.
Superior Biocompatibility
Unlike synthetic polymers or lipid-based systems that may trigger immune responses, our peptide carriers are composed of natural or modified amino acids, resulting in exceptionally low immunogenicity and toxicity.
Customizable Linker Chemistry
We offer a wide array of linkers, including cleavable and non-cleavable options, allowing for precise control over the timing and location of drug release based on the specific intracellular environment.
Frequently Asked Questions
Customer Review
"The team at CD BioGlyco provided exceptional support in developing a custom conjugate for our neurobiology project. The purity was higher than we had achieved with other vendors, and the endosomal escape efficiency in our primary neuron cultures was significantly improved."
– A.D., Institute of Neuroscience
"Their technical team suggested a specific cyclization strategy that increased our serum half-life by threefold. Their expertise in both peptide and nucleic acid chemistry is truly unique."
– E.P., Biopharmaceutical R&D Division
"The conjugation of our proprietary targeting peptide to a PNA cargo was handled with great care. The communication throughout the project was clear, and the final product performed exactly as expected in our targeting assays."
– D.J., Rare Disease Biotech
Associated Services
CD BioGlyco is committed to advancing the field of genetic medicine by providing high-performance delivery solutions. Our peptide-therapeutic oligonucleotide delivery service combines scientific innovation with industrial-grade reliability to help you overcome the most challenging delivery hurdles. Please feel free to contact us to help you design the optimal conjugate for your project.
Reference
- Järver, P.; et al. Peptide nanoparticle delivery of charge-neutral splice-switching morpholino oligonucleotides. Nucleic Acid Ther. 2015, 25(2): 65-77. (Open Access)