In vivo self-assembled small RNAs as a new generation of RNAi therapeutics

RNAi therapy has undergone two stages of development, direct injection of synthetic siRNAs and delivery with artificial vehicles or conjugated ligands; both have not solved the problem of efficient in vivo siRNA delivery. Here, we present a proof-of-principle strategy that reprogrammes host liver with genetic circuits to direct the synthesis and self-assembly of siRNAs into secretory exosomes and facilitate the in vivo delivery of siRNAs through circulating exosomes. By combination of different genetic circuit modules, in vivo assembled siRNAs are systematically distributed to multiple tissues or targeted to specific tissues (e.g., brain), inducing potent target gene silencing in these tissues. The therapeutic value of our strategy is demonstrated by programmed silencing of critical targets associated with various diseases, including EGFR/KRAS in lung cancer, EGFR/TNC in glioblastoma and PTP1B in obesity. Overall, our strategy represents a next generation RNAi therapeutics, which makes RNAi therapy feasible.

Insight Into the Prospects for RNAi Therapy of Cancer

RNA interference (RNAi), also known as gene silencing, is a biological process that prevents gene expression in certain diseases such as cancer. It can be used to improve the accuracy, efficiency, and stability of treatments, particularly genetic therapies. However, challenges such as delivery of oligonucleotide drug to less accessible parts of the body and the high incidence of toxic side effects are encountered. It is therefore imperative to improve their delivery to target sites and reduce their harmful effects on noncancerous cells to harness their full potential. In this study, the role of RNAi in the treatment of COVID-19, the novel coronavirus disease plaguing many countries, has been discussed. This review aims to ascertain the mechanism and application of RNAi and explore the current challenges of RNAi therapy by identifying some of the cancer delivery systems and providing drug information for their improvement. It is worth mentioning that delivery systems such as lipid-based delivery systems and exosomes have revolutionized RNAi therapy by reducing their immunogenicity and improving their cellular affinity. A deeper understanding of the mechanism and challenges associated with RNAi in cancer therapy can provide new insights into RNAi drug development.

A brief note on the scope of RNA interference(RNAi) therapy in mitigating COVID-19

Together with the use of number of repurposed/ repositioned antiviral drugs and immunomodulatory agents against the severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, currently several vaccines are under human trials to mitigate the COVID-19 worldwide. Although the drugs and vaccines appear to be effective in maximum cases or trials; however, the associated side effects, the required induction of the long-lasting immunity, and finally, the safety concerns are of significance in terms of their consistent application/ administration. A vast research on the SARS-CoV-2 genomics and on its similarities with SARS-CoV-1 and with the Middle East Respiratory Syndrome coronavirus (MERS-CoV) have unraveled the viral avoidance of the host immunity which creates a challenge in course of effective vaccine development although several COVID-19 vaccines are currently being used commercially worldwide. Such an unsteady circumstance led the scientists also to think on a new remedial approach i.e., the RNA interference (RNAi) therapy to inhibit the SARS-CoV-2 proliferation by degrading the viral RNAs. Present review discussed such strategy and its effectiveness during the ongoing COVID-19 pandemic.

Identification of a potent ionizable lipid for efficient macrophage transfection and systemic anti-Interleukin-1β siRNA delivery against acute liver failure

RNA interference (RNAi) therapy has great potential for treating inflammatory diseases. However, the development of potent carrier materials for delivering siRNA to macrophages is challenging. Herein, we design a set...