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Exosomes for circRNA Delivery

Exosomes for circRNA Delivery

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Circular RNAs (circRNAs) are a type of non-coding RNAs (ncRNAs) that are involved in post-transcriptional regulation. circRNAs are highly conserved and have a stable covalently closed continuous loop structure. CircRNAs naturally carried by exosomes have been widely used in cancer therapy, and their high delivery efficiency has greatly improved the therapeutic efficacy. Recent studies have shown that exogenous circular RNAs can act as templates for protein translation, allowing stable protein translation that bypasses cellular RNA sensors. Despite the possibility of immunogenicity, exosomal delivery of tumor-suppressing cyclic circRNAs may be a new cancer therapy.

circRNAs

circRNAs were originally thought to be intermediate products of intron lariats that have escaped degradation or by-products of aberrant splicing. With the development of detection technology and intensive research, it was found that circRNAs are molecules of ncRNAs consisting of hundreds or even thousands of nucleotides. These ncRNAs are formed by reverse splicing, mainly through noose structures or intron complementary pairing. Many tissues and cells express circRNAs, and the expression pattern of circRNAs varies depending on cell type and tissue as well as developmental stages. So far, there are more than 180,000 circRNAs are present in human transcriptomes, suggesting that circRNAs have unique regulatory mechanisms and cellular functions. Moreover, aberrantly expressed circRNAs have been demonstrated to be associated with carcinogenesis, where circRNAs serve as microRNA (miRNA) sponges, protein scaffolds, or new templates for protein translation.

Features of exosomal circRNAs

  • Enriched and stable in exosomes
  • Promote cellular proliferation
  • Contribute to tumor invasion and metastasis
  • Associated with chemotherapy resistance
  • Not only involved in intercellular communication between tumor cells, but also promote cancer cachexia.

Fig. 1 Biological functions of exosomal circRNAs.Fig. 1 Biological functions of exosomal circRNAs. (Seimiya, Takahiro, et al., 2022)

Delivery of therapeutic circRNA

circRNA is one of the emerging nucleic acid drugs. The special loop structure of circRNA not only prevents being degraded and improves circRNA expression and expression time, but also allows repeated administration. However, there are some challenges with the exosome-based delivery of exogenous circRNAs. On one hand, circRNAs have low circular efficiency. On the other hand, macromolecular circRNAs are difficult to load into the exosomes. To address these issues, the researchers have built relevant lentiviral vectors to properly and efficiently cyclize circRNAs and transfect them into target cells and load them into exosomes. More in-depth studies are needed to provide references for the application of exosome-mediated delivery of circRNA in disease.

Creative Proteomics is committed to providing innovative solutions to power your biological research. We are proud to offer a range of exosome research and analysis services. In addition to scalable upstream production and isolation of exosomes, we offer downstream processing for efficient exosome characterization and labeling to provide our customers with high quality exosomes. Notably, our services include the following services but are not limited to them. Our comprehensive, customized, and flexible services can greatly promote the application of exosomes as carriers for circRNA delivery.

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References

  1. Zhang, Ying, et al. "Recent advances in exosome-mediated nucleic acid delivery for cancer therapy." Journal of Nanobiotechnology 20.1 (2022): 1-29.
  2. Seimiya, Takahiro, et al. "Emerging roles of exosomal circular RNAs in cancer." Frontiers in cell and developmental biology 8 (2020): 568366.

* For Research Use Only. Not for use in diagnostic procedures.

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