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Delivery Method Development Service for RNAi


RNA interference (RNAi) has been demonstrated to be a potential therapeutic for many difficult-to-treat diseases such as viral infections and cancers. Equipped with world-leading technology platforms and professional scientific staff in the field of RNAi therapeutics development, Creative Biolabs provides a series of delivery systems for RNAi, including ligand-targeted delivery systems and chemical excipients-based delivery systems. We are pleased to share our extensive expertise to facilitate our clients’ research and project development.

The Background of RNAi Therapeutics

RNAi is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Taking advantage of the high selectivity and efficiency of this natural mechanism, RNAi has become an indispensable research tool for the analysis of gene functions. Moreover, it represents a promising new approach for producing gene-specific inhibition and knockouts, producing transgenic animal models, and designing new therapeutics. The primary barrier to its clinical applications is cell type-specific cytosolic delivery.

Small interfering RNA (siRNA) is a promising therapeutic solution to address gene overexpression or mutations as a post-transcriptional gene regulation process for several pathological conditions such as viral infections, cancer, genetic disorders, and autoimmune disorders like arthritis. However, naked siRNA is unstable in the bloodstream and cannot efficiently cross cell membranes besides being immunogenic. Therefore, careful design of the delivery systems is essential to fully utilize the potential of this therapeutic solution. siRNAs are densely negatively-charged macromolecules with a molecular weight of approximately 14 kDa. They generally can't cross the cell membrane by passive diffusions like many small molecules and ions. Moreover, siRNA trapped in endocytic compartments is susceptible to rapid degradation during endosome-lysosome trafficking, since most highly charged macromolecules are taken up by cells via endocytosis. In this regard, carriers that enable efficient siRNA delivery are required. A number of delivery technologies have been developed.

RNAi delivery strategies available for lymphocytes Figure 1. RNAi delivery strategies available for lymphocytes. (Mizrahy, 2017)

Delivery Systems for RNAi

Since siRNA is unstable in the bloodstream, protection methods must be developed to prolong its activity. Furthermore, the efficient and safe delivery of siRNA into target cells is critical for successful therapy. Accordingly, useful delivery methods should be designed to target siRNA to specific cells and to promote gene-silencing activity. Chemical modifications of siRNA have overcome problems associated with the instability of siRNA, and various ligands, including aptamer, peptides, antibodies and engineered antibody fragments, have considerable potential for targeted delivery of siRNA. The use of such ligands improves the efficiency, specificity, and consequently, the safety of the corresponding delivery systems. Ligand-targeted delivery systems have become one of the most common methods for siRNA delivery.

Although a large variety of siRNA delivery systems have been developed, lack of an efficient way to deliver siRNA to target tissue remains as an obstacle that retards the translation of siRNA for clinic use. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. In such a situation, various chemical excipients-based delivery systems have been paid more and more attention, such as nanoparticles, polymers, nucleic acid nanostructures, exosomes and N-acetylgalactosamine (GalNAc) delivery systems.

Service

RNAi therapeutics offer several advantages over the traditional small molecules and protein-based drugs. They could virtually target any genes with high selectivity, including those “undruggable” targets. Creative Biolabs is one of the well-recognized experts who are professional in the field of RNAi therapeutics development. With years of experience, our scientists offer high-quality service in the development of short dsRNA delivery systems for RNAi to meet our clients’ demands precisely.

Highlights

Creative Biolabs is committed to providing high-quality service in the development of short dsRNA delivery systems for RNAi. We offer turn-key or ala carte services customized to our client’s needs. Please contact us for more information and a detailed quote.

Reference

  1. Mizrahy, S.; et al. (2017). Current progress in non-viral RNAi-based delivery strategies to lymphocytes. Mol Ther. 5(7):1491-1500.

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