Both aptamer and sequence-specific gene-silencing ability of small interfering RNA (siRNA) has been exploited as new therapeutic approaches for the treatment of a variety of diseases, and have been validated with a product in the market. However, efficient and safe delivery of siRNA into target cells is still a challenge in clinical development. Recently, aptamer-siRNA chimeras have emerged to enhance the RNAi efficacy of siRNA via targeted delivery. Seasoned scientists at Creative Biolabs are proficient at engineering cancer cells with aptamer-siRNA chimeras for enhanced antitumor Tcell immunity.
Immunotherapy benefits some aggressive cancers but lacks effectiveness in most. Novel strategies to increase cancer immunogenicity are needed to improve immunotherapy. The most successful current immune therapies use checkpoint blockade to restore functionality to exhausted tumor-infiltrating lymphocytes (TIL) or adoptively transferred, cytotoxic T cells expressing chimeric receptors (CAR T cells) that kill tumor cells. However, no CAR T cell therapy is approved for solid tumors, and only a minority of solid tumors respond to checkpoint blockade. Since some tumors are not recognized by immune cells as foreign, they do not respond to checkpoint inhibition. Tumors only respond when there are high somatic mutation rates, which contribute to their immunogenicity by causing the tumor to express nonself-tumor antigens. Much of the ongoing work to improve responses focuses on combining checkpoint inhibitors, with some successes, but with the risk of increased autoimmune toxicity. This is because most checkpoint inhibitors remove the brakes not on normal T cells but also antitumor T cells. In recent years, synthetic aptamers have emerged as effective delivery tools for many therapeutic oligonucleotide-based drugs, including siRNAs. Aptamer-siRNA chimeras represent a novel promising approach to cancer therapy.
Fig.1 Aptamer-siRNA designs. (Kruspe & Giangrande, 2017)
To evaluate new ways to make tumors susceptible to immune control, Creative Biolabs took advantage of aptamer-siRNA chimeras for tumor-directed in vivo gene knockdown to enhance antitumor T cell immunity. Creative Biolabs has developed cutting-edge aptamer selection technology, which has made possible the identification of cell-specific, cell-internalizing aptamers for the cell-targeted delivery of therapeutic oligonucleotides.
Our scientists are also proficient at the design of aptamer-siRNA chimeras and we employ several strategies for aptamer-siRNA conjugation, including the use of acid labile or redox-sensitive linkers, or “universal” linker to form “sticky-bridge”.
Creative Biolabs has accumulated rich experience in Engineering Cancer Cells with aptamer-siRNA chimeras and employing RNA aptamers as carriers for cell-targeted siRNA delivery. We offer highly customized solutions according to our clients’ needs. For more detailed information, please feel free to contact us or directly send us an inquiry.
Reference
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