Adenoviral Vector Design for RNAi Delivery

Adenoviral vectors have become an important tool for human gene therapy and have demonstrated high transduction efficiency in a broad range of target tissues with a good safety profile in animal models and human clinical trials. RNA interference (RNAi) has emerged as another important tool for human gene therapy, enabling scientists to move from classical gene transfer to gene silencing approaches, or combinations thereof. The key challenge for achieving effective RNAi is its delivery to the desired organs and target cells. Till now, the RNAi technique based adenoviral vectors has been used successfully in a variety of cells and tissues. Creative Biolabs has been occupied in the research of gene therapy for years and focuses on the field of human diseases research with a professional adenovirus vector construction platform that can help you with gene therapy development.

Introduction of RNAi Delivery

RNAi is a natural mechanism of gene silencing conserved in plant and mammalian cells. RNAi induces both initiation and effector steps. RNAi is initiated by double-stranded RNA, which is cleaved by the ribonuclease III-type enzyme Dicer (Dcr) into siRNAs-short 21-23 nt duplexes with a symmetric 2 nt overhang at the 3'-end and a 5'-phosphate and 3'-hydroxy group. This siRNA molecule is mixed into a nuclease-containing multi-protein complex, known as RNA-induced silencing complex (RISC). This is activated by an RNA helicase activity upon the loss of one strand of the siRNA duplex. In the effector steps, the single-stranded siRNA guides post-transcriptional gene silencing by the degradation of their target mRNA or by inducing translational inhibition through the miRNA pathway. Most adenoviral vectors used in RNAi delivery are derived from human serotypes 2 and 5, the commonly used adenoviruses in gene therapy. In general, siRNA delivery strategy is driven by H1-RNA promoter, while RNA pol II CMV promoter has been demonstrated to mediate gene silencing both in vitro and in vivo. The adenoviral vector expressing si/sh RNA has been demonstrated to be highly effective in islet β-cells, cardiovascular cells, and lung cancer cell lines. What's more, the regulated adenoviral vectors offer the advantages of not only being able to infect a wide array of replicating and non-replicating cells but allowing temporal control of gene silencing.

Figure 1. Genome structures of adenoviruses and schematic structure of adenoviral vector for shRNA.

Service

There is a high potential for clinical use of RNAi in the treatment of a wide variety of human diseases, including genetic disorders, infectious diseases, and cancers. The delivery and target specificity of siRNA are the keys in gene therapy. At present, the most efficient methods of RNAi remain with the adenoviral vectors. It is very important to determine the vector that is most suitable for each special therapeutic application or even each individual patient. Therefore, we offer a large collection of adenovirus vector design services including, but not restricted to, inducible, tissue-specific, hybrid, oncolytic and high-throughput RNAi vectors based on adenoviruses.

Creative Biolabs has long-term devoted to the development of gene therapies for years. With extensive experience, our scientists have developed several adenovirus vector construction platforms to promote customers project goals. We are pleased to use our advanced platforms to offer the best service and the most qualified products to satisfy diverse needs from our customers. If you are interested in our services, please contact us for more details.