bims-limsir Biomed News
on Lipophilic modified siRNAs
Issue of 2023–03–05
two papers selected by
Ivan V. Chernikov, Institute of Сhemical Biology and Fundamental Medicine of the SB RAS
  1. Single-cell quantification and dose-response of cytosolic siRNA delivery.
  2. Current clinical trials with non-coding RNA-based therapeutics in malignant diseases: A systematic review.
  1. Nat Commun. 2023 Feb 25. 14(1): 1075
    Single-cell quantification and dose-response of cytosolic siRNA delivery.
    Hampus Hedlund, Hampus Du Rietz, Johanna M Johansson, Hanna C Eriksson, Wahed Zedan, Linfeng Huang, Jonas Wallin, Anders Wittrup.
      Endosomal escape and subsequent cytosolic delivery of small interfering RNA (siRNA) therapeutics is believed to be highly inefficient. Since it has not been possible to quantify cytosolic amounts of delivered siRNA at therapeutic doses, determining delivery bottlenecks and total efficiency has been difficult. Here, we present a confocal microscopy-based method to quantify cytosolic delivery of fluorescently labeled siRNA during lipid-mediated delivery. This method enables detection and quantification of sub-nanomolar cytosolic siRNA release amounts from individual release events with measures of quantitation confidence for each event. Single-cell kinetics of siRNA-mediated knockdown in cells expressing destabilized eGFP unveiled a dose-response relationship with respect to knockdown induction, depth and duration in the range from several hundred to thousands of cytosolic siRNA molecules. Accurate quantification of cytosolic siRNA, and the establishment of the intracellular dose-response relationships, will aid the development and characterization of novel delivery strategies for nucleic acid therapeutics.
    DOI:  https://doi.org/10.1038/s41467-023-36752-1
  2. Transl Oncol. 2023 Feb 23. pii: S1936-5233(23)00020-7. [Epub ahead of print]31 101634
    Current clinical trials with non-coding RNA-based therapeutics in malignant diseases: A systematic review.
    Masaoki Ito, Yoshihiro Miyata, Morihito Okada.
      This systematic review aimed to shed light on the trend of current clinical trials of non-coding RNA (ncRNA)-based therapeutics for malignant diseases. We conducted a database search for published literature and ongoing clinical trials using PubMed, clinicaltrials.gov, and University Medical Information Network (UMIN) clinical trial registry. To ensure that our review was based on up-to-date clinical trials, we limited our search to literature published within the last five years (January 2017-September 2022). Furthermore, due to the "clinical" nature of our review, we focused only on studies involving human participants. Among ncRNAs, microRNAs have been extensively explored in observational studies of malignant diseases as potential diagnostic markers and prognostic predictors, as well as for their therapeutic monitoring and profiling capabilities. As therapeutic agents, microRNA or siRNA were estimated in interventional human clinical trials and showed promising outcomes; however, the number of trials was small. Evidence and ongoing clinical trials in which ncRNAs other than microRNA or siRNA have been evaluated for their potential as therapeutic agents are limited. Here, we summarized microRNA as a potential therapeutic agent in malignant diseases, but most of the current evidence suggests that it is useful as a potential biomarker. siRNA is also a promising ncRNA technique in cancer, however more data from clinical trials are warranted for clinical use.
    Keywords:  Cancer; Clinical trial; Malignant diseases; MicroRNA; Non-coding RNA; RNA interference
    DOI:  https://doi.org/10.1016/j.tranon.2023.101634
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