The CRISPR/Cas9 system has been applied in the genome editing and disruption of latent infections for herpesviruses such as the herpes simplex virus, Epstein–Barr virus, cytomegalovirus, and Kaposi’s sarcoma-associated herpesvirus. CRISPR/Cas9-directed mutagenesis can introduce similar types of mutations to the viral genome as can bacterial artificial chromosome recombination engineering, which maintains and reconstitutes the viral genome successfully. The cleavage mediated by CRISPR/Cas9 enables the manipulation of disease-associated viral strains with unprecedented efficiency and precision. Additionally, current therapies for herpesvirus productive and latent infections are limited in efficacy and cannot eradicate viruses. CRISPR/Cas9 is potentially adapted for antiviral treatment by specifically targeting viral genomes during latent infections. This review, which focuses on recently published progress, suggests that the CRISPR/Cas9 system is not only a useful tool for basic virology research, but also a promising strategy for the control and prevention of herpesvirus latent infections.
Opioid addiction is a chronic and complex disease characterized by relapse and remission. In the past decade, the opioid epidemic or opioid crisis in the United States has raised public awareness. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Classic and molecular genetic research has provided valuable information and revealed the possible mechanism of individual differences in vulnerability for opioid addiction. The polygenic risk score based on the results of a genome-wide association study (GWAS) may be a promising tool to evaluate the association between phenotypes and genetic markers across the entire genome. A novel gene editing approach, clustered, regularly-interspaced short palindromic repeats (CRISPR), has been widely used in basic research and potentially applied to human therapeutics such as mental illness; many applications against addiction based on CRISPR are currently under research, and some are successful in animal studies. In this article, we summarized the biological mechanisms of opioid addiction and medical treatments, and we reviewed articles about the genetics of opioid addiction, the promising approach to predict the risk of opioid addiction, and a novel gene editing approach. Further research on medical treatments based on individual vulnerability is needed.
Nucleic acid-based gene interfering approaches, such as those mediated by RNA interference and RNase P-associated external guide sequence (EGS), have emerged as promising antiviral strategies. The RNase P-based technology is unique, because a custom-designed EGS can bind to any complementary mRNA sequence and recruit intracellular RNase P for specific degradation of the target mRNA. In this study, a functional EGS was constructed to target hepatitis B virus (HBV) essential transcripts. Furthermore, an attenuated Salmonella strain was constructed and used for delivery of anti-HBV EGS in cells and in mice. Substantial reduction in the levels of HBV gene expression and viral DNA was detected in cells treated with the Salmonella vector carrying the functional EGS construct. Furthermore, oral inoculation of Salmonella carrying the EGS construct led to an inhibition of ~95% in the levels of HBV gene expression and a reduction of ~200,000-fold in viral DNA level in the livers and sera of the treated mice transfected with a HBV plasmid. Our results suggest that EGSs are effective in inhibiting HBV replication in cultured cells and mammalian livers, and demonstrate the use of Salmonella-mediated delivery of EGS as a promising therapeutic approach for human diseases including HBV infection.
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