Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections

Abstract

Several viruses cause pulmonary infections due to their shared tropism with cells of the respiratory tract. These respiratory problems due to viral infection become a public health concern due to rapid transmission through air/aerosols or via direct-indirect contact with infected persons. In addition, the cross-species transmission causes alterations to viral genetic makeup thereby increasing the risk of emergence of pathogens with new and more potent infectivity. With the introduction of effective nucleic acid-based technologies, post translational gene silencing (PTGS) is being increasingly used to silence viral gene targets and has shown promising approach towards management of many viral infections. Since several host factors are also utilized by these viruses during various stages of infection, silencing these host factors can also serve as promising therapeutic tool. Several nucleic acid-based technologies such as short interfering RNAs (siRNA), antisense oligonucleotides, aptamers, deoxyribozymes (DNAzymes), and ribozymes have been studied and used against management of respiratory viruses. These therapeutic nucleic acids can be efficiently delivered through the airways. Studies have also shown efficacy of gene therapy in clinical trials against respiratory syncytial virus (RSV) as well as models of respiratory diseases including severe acute respiratory syndrome (SARS), measles and influenza. In this review, we have summarized some of the recent advancements made in the area of nucleic acid based therapeutics and highlighted the emerging roles of nucleic acids in the management of some of the severe respiratory viral infections. We have also focused on the methods of their delivery and associated challenges.

Inhaled RNA Therapy: From Promise to Reality

“…There is an increasing number of studies that report the potential of RNA in treating a range of lung diseases including asthma [ 4 ], cystic fibrosis (CF) [ 5 ], lung cancer [ 6 ], and respiratory infections [ 7 ]. Inhalation of aerosol is an efficient way to deliver RNA to the lung by maximizing local concentration while minimizing systemic exposure.…”

Nucleic acid-based therapy for coronavirus disease 2019

“…Among them, the nucleic acid-based therapeutic molecules have shown significant potential as therapeutic agents with potential anti-viral properties [12]. These proposed anti-viral drugs, feature a versatile mode of action and has been designed to specifically arrest viral disease progression [13]. The nucleic acid-based drugs have been shown to elicit a broad spectrum of anti-viral immunity in the body along with suppressing viral replication and gene expression [14].…”

“…Several viruses have been reported to show tropism towards the cells of respiratory tracts which not only help in the entry of virus particles inside respiratory tracts but it also helps to causes the infection in the host cells [13]. The physiological function of the lungs makes it highly exposed to pollutants and viral particles from outside [13]. Due to this reason, lungs get susceptible to several diseases ranging from common viral infection to lung cancer.…”

“…Due to this reason, lungs get susceptible to several diseases ranging from common viral infection to lung cancer. Viruses that infect the respiratory tract spread rapidly among the population due to their simple and easy mode of transmission [13]. The transmission of such viruses mainly takes place either by physical contact with the infected person or by droplets containing the viral particles [13].…”

Generation of ssDNA aptamers as diagnostic tool for Newcastle avian virus

“…Similarly, characterization of aptamers against other viruses including respiratory syncytial virus (RSV), severe acute respiratory syndrome virus (SARS) and measles virus have already been reported [ 16 ]. However, to date there is no reports on aptamers developed for avian virus detection.…”