Viral Vectors Applied for RNAi-Based Antiviral Therapy

Lundström, Kenneth

doi:10.3390/v12090924

Cited by 29 publications

(17 citation statements)

References 100 publications

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“…The plasmids or virus vectors-based shRNAs are much more stable than RNAs in certain environments and can be processed by a host cellular mechanism to continuously produce siRNAs in the host cells, which can overcome the disadvantages of chemically synthesized siRNAs [ 21 ]. Specifically, viral vectors, including lentiviruses, adenovirus, and other self-replicating RNA viruses, could trigger long-term inhibition activity [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Plasmids Expressing shRNAs Specific to the Nucleocapsid Gene Inhibit the Replication of Porcine Deltacoronavirus In Vivo

et al. 2021

Animals

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Porcine deltacoronavirus (PDCoV) is a novel enteric coronavirus and is becoming one of the major causative agents of diarrhea in pig herds in recent years. To date, there are no commercial vaccines or antiviral pharmaceutical agents available to control PDCoV infection. Therefore, developing a reliable strategy against PDCoV is urgently needed. In this study, to observe the antiviral activity of RNA interference (RNAi), four short hairpin RNAs (shRNAs) specific to the nucleocapsid (N) gene of PDCoV were designed and tested in vitro. Of these, a double-shRNA-expression vector, designated as pSil-double-shRNA-N1, was the most effectively expressed, and the inhibition of PDCoV replication was then further evaluated in neonatal piglets. Our preliminary results reveal that plasmid-based double-shRNA-expression targeting the N gene of PDCoV can significantly protect LLC-PK1 cells and piglets from pathological lesions induced by PDCoV. Our study could benefit the investigation of the specific functions of viral genes related to PDCoV infection and offer a possible methodology of RNAi-based therapeutics for PDCoV infection.

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Section: Discussionmentioning

confidence: 99%

Plasmids Expressing shRNAs Specific to the Nucleocapsid Gene Inhibit the Replication of Porcine Deltacoronavirus In Vivo

et al. 2021

Animals

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“…Consequently, newer alternative therapeutic approaches are actively explored world-wide. In recent years, several oligonucleotide-based therapies such as short interfering RNAs (siRNA), microRNAs, aptamers, DNAzymes, and ribozymes have been used for diagnosis and/or treatment of viral diseases ( Kim and Lee, 2021 , Lundstrom, 2020 ). Among these nuclei-acid based approaches, DNA or RNA aptamers have been increasingly gaining wide attention due to their efficacy and specificity to pathogens and ease in their production by complete chemical synthesis methods.…”

Section: Application Of Aptamers In the Targeted Drug Delivery And Treatment Of Animal Diseasesmentioning

confidence: 99%

Aptamer-based diagnostic and therapeutic approaches in animals: Current potential and challenges

Devi

Sharma

Ahmed

et al. 2021

Saudi Journal of Biological Sciences

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Fast and precise diagnosis of infectious and non-infectious animal diseases and their targeted treatments are of utmost importance for their clinical management. The existing biochemical, serological and molecular methods of disease diagnosis need improvement in their specificity, sensitivity and cost and, are generally not amenable for being used as points-of-care (POC) device. Further, with dramatic changes in environment and farm management practices, one should also arm ourselves and prepare for emerging and re-emerging animal diseases such as cancer, prion diseases, COVID-19, influenza etc. Aptamer – oligonucleotide or short peptides that can specifically bind to target molecules – have increasingly become popular in developing biosensors for sensitive detection of analytes, pathogens (bacteria, virus, fungus, prions), drug residues, toxins and, cancerous cells. They have also been proven successful in the cellular delivery of drugs and targeted therapy of infectious diseases and physiological disorders. However, the in vivo application of aptamer-mediated biosensing and therapy in animals has been limited. This paper reviews the existing reports on the application of aptamer-based biosensors and targeted therapy in animals. It also dissects the various modifications to aptamers that were found to be successful in in vivo application of the aptamers in diagnostics and therapeutics. Finally, it also highlights major challenges and future directions in the application of aptamers in the field of veterinary medicine.

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“…The small interfering RNAs (siRNAs), are a promising approach for gene therapy, however their intracellular administration remains difficult. To date, a great variety of delivery system for siRNAs has been investigated such as lipids, polymers, aptamers and cell penetrating peptides (CPPs) [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. In this regard, CPPs appear as a new class of transporters, which increase intracellular uptake of biologically active molecules including siRNAs [ 45 ] ( Figure 2 ).…”

Section: Benefit Of Cpps Used As Vehicles In Oligonucleotides Delimentioning

confidence: 99%

“…RNA interference is an endogenous process in which siRNAs post-transcriptionally regulate gene expressions [ 24 ]. Because of its exceptional roles in regulating the functions and stabilities of mRNAs, siRNA has emerged as a promising alternative therapeutic approach for the treatment of viral diseases including chronic HBV infection [ 25 , 26 , 27 , 28 ]. However, the synthetic siRNAs specifically targeting HBV need to be delivered into the hepatocytes to silence viral genes.…”

Section: Introductionmentioning

confidence: 99%

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

et al. 2020

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Peptide Nucleic Acid (PNAs) and small noncoding RNAs including small interfering RNAs (siRNAs) represent a new class of oligonucleotides considered as an alternative therapeutic strategy in the chronic hepatitis B treatment. Indeed, chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide, despite the availability of an effective prophylactic vaccine. Current therapeutic approaches approved for chronic HBV treatment are pegylated-interferon alpha (IFN)-α and nucleos(t)ide analogues (NAs). Both therapies do not completely eradicate viral infection and promote severe side effects. In this context, the development of new effective treatments is imperative. This review focuses on antiviral activity of both PNAs and siRNAs targeting hepatitis B virus. Thus, we briefly present our results on the ability of PNAs to decrease hepadnaviral replication in duck hepatitis B virus (DHBV) model. Interestingly, other oligonucleotides as siRNAs could significantly inhibit HBV antigen expression in transient replicative cell culture. Because the application of these oligonucleotides as new antiviral drugs has been hampered by their poor intracellular bioavailability, we also discuss the benefits of their coupling to different molecules such as the cell penetrating peptides (CPPs), which were used as vehicles to deliver therapeutic agents into the cells.

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Viral Vectors Applied for RNAi-Based Antiviral Therapy

Cited by 29 publications

References 100 publications

Plasmids Expressing shRNAs Specific to the Nucleocapsid Gene Inhibit the Replication of Porcine Deltacoronavirus In Vivo

Plasmids Expressing shRNAs Specific to the Nucleocapsid Gene Inhibit the Replication of Porcine Deltacoronavirus In Vivo

Aptamer-based diagnostic and therapeutic approaches in animals: Current potential and challenges

Cell Penetrating Peptides Used in Delivery of Therapeutic Oligonucleotides Targeting Hepatitis B Virus

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