Peptide-siRNA Conjugation
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Small interfering RNA (siRNA) conjugate refers to siRNA linked to another molecule, usually peptides, lipids, or antibodies. 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. Peptide-siRNA Conjugation technology is to use peptides as a carrier of nucleic acids to bring short siRNA into the body, exert its gene silencing effect, and specifically silence the expression of target genes to achieve therapeutic purposes. Additionally, these conjugations can also alter the tissue distribution or intracellular localization of siRNA, enhancing their therapeutic efficacy. This technique stands as a groundbreaking method in the field of genomic medicine. Creative Peptides specializes in providing high-quality and reliable peptide-siRNA conjugation services to support various research and development projects.
Fig. 1 Efficient siRNA-peptide conjugation for specific targeted delivery into tumor cells. (Gandioso, A., 2017)
Advantages of Peptide-siRNA Conjugation
Delivery is a major challenge for the effective use of siRNA, as these molecules are notoriously difficult to get across cellular membranes. SiRNA may be highly potent and specific, but it is also instable and easy to be degraded. Thus, without a means of effective delivery, its therapeutic potential remains limited. Peptide-siRNA conjugate can avoid such shortcomings of siRNA. Peptide-siRNA Conjugation plays an important role in antisense therapy. Peptides in these materials target cells, uptake and endosome escape, and play an important role in the catalytic cleavage of intracellular RNA.
Enhance Cell Penetration: By conjugation of siRNA with peptide, the specific properties of peptide (such as cell penetration peptide) can be used to improve the ability of siRNA to enter cells. This helps to overcome the obstacles of siRNA transmission in cells, thus increasing its concentration and activity in target cells.
Increased Stability: Peptides can increase the stability of siRNA, preventing it from being degraded in the biological environment. This means that the siRNA can remain active for a longer period of time.
Targeted Therapy: Peptides can serve as efficient delivery vehicles for siRNA. They can allow for the targeted delivery of siRNA to specific tissues or cell types, thus greatly enhancing the efficiency and reducing potential off-target effects.
Efficient Gene Silencing: Conjugation of peptides to siRNA can increase the efficiency of gene silencing. This can be beneficial in therapeutic applications where it's necessary to switch off certain genes.
Avoidance of Immune Response: In comparison to viral vectors, using peptide-siRNA conjugates for delivery can potentially avoid the triggering of an immune response.
Multifunctional: Peptides can carry a variety of functional groups, which enables Peptide-siRNA conjugates to achieve multiple functions at the same time. For example, fluorescent groups can be introduced into peptide segments for tracing, or other therapeutic molecules can be introduced to achieve synergistic therapy.
Easy to Synthesize and Modify: Compared with other carrier systems, peptide segments usually have simpler synthetic routes and higher purity. In addition, the chemical properties of peptide make it easy to be modified and optimized to meet different therapeutic needs.
Applications of Peptide-siRNA Conjugates
The alkyne group and the azide group are introduced into the siRNA as the effector molecule and the polypeptide as the molecule, and then the chemical reaction is clicked to form a uniform and stable compound.
Peptide-siRNA Conjugation, as a specific targeted drug, can be used for targeted therapy of tumors. The researchers discovered a new method for efficiently synthesizing a cell-penetrating peptide-small interfering RNA (CPP-siRNA) covalent conjugate, and confirmed that the covalent conjugate can achieve effective intracellular delivery of siRNA and gene silencing. The covalent binding of peptides can not only increase the efficiency of siRNA accumulation in cells, but also ensure the specificity of its role in target cells. Different targeting peptides are conjugated to siRNA, and such conjugates are biologically active both in vitro and in vivo.
Fig. 2 CPPs for siRNA delivery. (A) Covalently conjugated siRNA with CPP. (B) siRNA complexed with the CPP and (C) CPP-decorated nanoparticle. (Ali Z., 2023)
- Treating Genetic Disorders
Many genetic disorders are caused by mutations that result in the production of harmful proteins. Peptide-siRNA conjugates can be used to specifically downregulate these harmful proteins.
Study on gene function: siRNA is an important tool to study gene function, and conjugates can improve the transmission efficiency and cell penetration of siRNA, which is helpful to further study the role of genes in organisms.
Biological imaging and tracing: by introducing fluorescent groups or other imaging molecules into peptide segments, conjugates can be used for biological imaging and tracing research, helping scientists better understand the distribution and metabolic process of drugs in vivo.
Peptide-siRNA conjugates have potential application in the treatment of HIV, by specifically targeting and silencing HIV genes.
These conjugates can be used to target and silence genes associated with neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's diseases.
Peptide-siRNA conjugates could also be used to treat eye-related genetic diseases, such as age-related macular degeneration, by silencing the genes responsible for the disease.
Our Services
Creative Peptides has scientific research personnel with many years of Peptide-siRNA Conjugation synthesis experience, providing customers with high-efficiency, high-quality peptides, while having a global competitive price advantage to meet customers' scientific research needs. We offer services include:
- Coupling of tumor related receptor peptide to siRNA
- Customized Peptide-siRNA Conjugation
- purification of the conjugate via special HPLC gradients
- Characterization and verification of the conjugate with mass spectrometry and analytical HPLC and CE
Our Advantages
Throughout the synthesis process, every conjugate is closely observed and managed in accordance with our strict quality assurance and control guidelines. Gel electrophoresis is used to test purity, whereas mass spectrometry is used to identify the finished product.
- Fully traceable documentation system
- Innovative products
- High quality service
- High repeatability between batches
- Product quality is stable and reliable
- Low sales price
More About SiRNA Conjugates
SiRNA mediating sequence-specific mRNA degradation is a mechanism called RNA interference (RNAi), which is a main cellular mechanism regulating gene expression, has now become a promising therapeutic platform for treating multiple illnesses caused by inappropriate gene activity at high effectiveness, such as cancer. Nevertheless, the main obstacles related to biological instability and low delivery efficiency have impeded the clinical translation of siRNA therapies. Cationic lipids and polymers were used to be one of siRNA delivery strategies to prolong pharmacokinetics and delivery efficiency.
But several disadvantages still limit cationic nanocarriers, such as non-specific protein adsorption, high liver accumulation, and severe toxicity. In this case, peptide-siRNA conjugation has been discovered to be a promising strategy. It is a carrier-free bioconjugation which consists of biocompatible molecules. Conjugated with peptides, siRNA is able to transfer RNAi to tissues beyond the liver, making it more possible to be applied in clinical. Even so, there are still a few limitations of siRNA conjugates, like low bioavailability and adverse pharmacokinetics. These restrictions result from the requirement that siRNA be absorbed into the target tumor cells' cytoplasm following injection. Therefore, to make siRNA conjugates be acceptable to clinical application, this technique need overcome these shortcomings such as tumor tissue penetration, targeting heterogeneous tumor cell surface and endosomal escape wherein the siRNA can be faced during tumor-targeted delivery and eliciting therapeutic effects. For instance, in a previous study, researchers found a type of peptide carriers which can deliver siRNA selectively into HER2+ breast cancer cell lines, using a simple technique for adding peptides of various length and complexity to siRNAs in order to click functionalize them.
FAQ
1. How does peptide-siRNA conjugation enhance targeted gene therapy?
The ability of peptides to target specific cell types or tissues enhances the delivery of siRNA, which plays a crucial role in gene silencing. The conjugation enhances cell uptake, improves endosomal escape, and allows targeted delivery with minimal off-target effects.
2. What challenges exist in peptide-siRNA conjugation technology?
The main challenges include the efficient synthesis of stable peptide-siRNA conjugates, the selection of appropriate peptides, and the potential immune responses to dsiRNAs-peptide conjugates. Moreover, understanding the fate of peptide-siRNA conjugates inside cells and optimizing the stability in physiological conditions are also significant.
3. How is the stability of peptide-siRNA conjugates determined?
The stability is usually determined by serum stability assays, where the conjugates are incubated with serum and the amount of intact conjugate is measured over time. Another approach is the use of nuclease resistance assays, where the resistance to enzymatic degradation of the conjugate is assessed.
4. What are common methods used to conjugate peptides to siRNA?
Two common methods are the use of covalent bonds or non-covalent bonds. Covalent methods involve chemical reactions that create a stable bond between the peptide and the siRNA, while non-covalent methods involve the use of physical forces or biological interactions.
References
- Ali Z., et al. Engineering siRNA therapeutics: challenges and strategies. Journal of Nanobiotechnology. 2023, 21(1): 381.
- Chernikov, I. V., et al. Current development of siRNA bioconjugates: from research to the clinic. Frontiers in Pharmacology. 2019,10: 452642.
- Lee, J. W., et al. Molecularly engineered siRNA conjugates for tumor-targeted RNAi therapy. Journal of Controlled Release. 2022, 351: 713-726.
- Gandioso, A., et al. Efficient siRNA-peptide conjugation for specific targeted delivery into tumor cells. Chemical Communications. 2017,53(19): 2870-2873.
