Abstract
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.
Highlights
Introduction iationsAccording to data by WHO, as of 31 January 2022, over 373 million people worldwide have been infected with severe acute respiratory syndrome (SARS)-CoV-2, and there have been more than 5.6 million confirmed deaths due to this virus since December 2019
This review focuses on summarizing the therapeutic role of small interfering RNAs (siRNAs) in COVID-19 disease
We discuss a variety of potential nanocarriers, including organic nanoparticles, such as lipid NPs, polymer NPs, and glycogen NPs, and inorganic nanoparticles, such as gold NPs and magnetic NPs; we summarize the progress of these platforms in siRNA delivery
Summary
NPs are valuable carriers to deliver functional nucleic acid fragments into the body for specific targeted therapy. Other types of LNPs have been used to deliver siRNA, including solid LNPs (SLNs) [148], nanostructured lipid carriers (NLCs) [149], nonlamellar LNPs (NLNs) [150], ethosomes [151], and echogenic liposomes [152] (Table 2) These LNPs could improve the stability of siRNA and effectively release siRNA after entering the target cells [127]. The addition of some cofactors may improve the delivery efficiency and gene silencing effect of siRNA PNPs. To evaluate the effect of siRNA PNPs against SARS-CoV-2 in vitro and in vivo, Khaitov et al identified the most effective siRNA (siR-7) from 15 candidate siRNAs. After adding locked nucleic acids (LNAs) to enhance its stability, it was assembled with peptide dendrimer KK-46 (to form siR-7-EM/KK-46 complex). The value of GNPs in COVID-19 needs further exploration
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