siRNA-Peptide Conjugation Service
Introduction to siRNA Bioconjugation
RNA interference (RNAi) is the sequence-specific gene silencing phenomenon mediated by small interference RNA (siRNA), which has been widely investigated for application in human disease treatment. Owing to the large molecular weight and strong anionic charge of siRNA molecule, the transmembrane capability of naked siRNA is inadequate and it has limited siRNA's clinical application[1]. One of the most promising approaches to solve the problem of the inadequate transmembrane capability of naked siRNA is bioconjugation; the covalent connection of siRNAs with biogenic molecules (lipophilic molecules, antibodies, aptamers, ligands, peptides, or polymers). Bioconjugates are "ideal nanoparticles" since they do not need a positive charge to form complexes, are less toxic, and are less effectively recognized by components of the immune system because of their small size[2].
The most commonly used types of bioconjugates (WANG, 2013)
siRNA and Peptide Conjugates
Due to the endogenous transport mechanism, some proteins and peptides can penetrate the cell and transfer other molecules into the cell. The main mechanisms of peptide transport include binding to surface proteins, glycoconjugates or anionic cellular lipids, followed by absorption through endocytosis, membrane penetration, membrane lysis, or pore formation in the membrane. There are two main methods for obtaining such peptides: using phage display, or using proteins that perform similar functions in nature. The ability of peptides to specifically interact with certain proteins on the cell surface due to specific elements in their tertiary structure is used for targeted delivery of siRNA[2].
Different targeted peptides have been conjugated to siRNAs and such conjugates have been proved to improve their in vivo pharmacokinetic behavior, for example, increasing the biological duration and delivery efficiency while maintaining gene silencing activity. Cell penetrating peptides (CPPs) are a novel type of membrane translocation agent for macromolecules intracellular delivery. The direct conjugation of CPPs to antisense oligonucleotides, peptide nucleic acid (PNA) and siRNA have improved their intracellular delivery[1].
siRNA–peptide conjugation (Albert Gandioso, 2017)
Our siRNA-Peptide Conjugation Services
With our advanced synthesizers and over a decade of experience in nucleic acid drug development, Creative Biolabs can provide customized siRNA-peptide conjugates for a variety of biological applications, such as cell screening, antibody production, therapeutic research and in vivo research and more.
Modifications (If any modification you are looking for is not on the list, please contact us.):
Oligo |
Peptide |
| Phosphorothioate linkage | Acetylation |
| Dye labeling (FAM, HEX ,TET, etc) | Phosphorylation |
| Biotinylation | methylation |
| Spacer (C3, HEG, etc) | Biotinylation |
| 2'-O-methyl RNA | Spacer (Ahx, AEEAc, etc) |
| Fatty acids conjugation | |
| Dye-Labeling (FAM, TAMRA, etc) |
Quality Assurance
During synthesis, each siRNA-peptide conjugate undergoes strict quality control, identified by mass spectrometry, and its high purity is ensured by high-throughput gel electrophoresis, high-performance liquid chromatography or other appropriate QC methods.
Advantages:
- Quality oligo synthesis
- A wide choice of target molecules
- Different modifications available
- High yield
- High purity: Generally above 85-95%
- Various QC methods
- Micrograms to grams-scale
- Length of siRNA conjugates: 10 - 40 bases
- Length of peptides: 5-22 amino acids
Delivery Specifications:
- Lyophilized sample
- COA
- MS/HPLC report
Since its establishment, Creative Biolabs has developed quality products with advanced technologies, and has made considerable progress in the development of oligonucleotide drugs, large-scale production of oligonucleotides, raw material drug quality research, GMP production line construction and GMP management. You can contact us for any oligonucleotide drug research and development needs.
References
- WANG XiaoFeng, Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker. SCIENCE CHINA Chemistry. 2013 56 11: 1542-1549
- Ivan V. Chernikov, Current Development of siRNA Bioconjugates: From Research to the Clinic. Front. Pharmacol., 26 2019
*For Research Use Only. Not for use in diagnostic procedures.