In vitro transcribed mRNA for expression of designer nucleases: Advantages as a novel therapeutic for the management of chronic HBV infection
| Autor: | Patrick Arbuthnot, Abdullah Ely, Tiffany S. Smith, Prashika Singh |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Genetic Vectors
Pharmaceutical Science 02 engineering and technology medicine.disease_cause Antiviral Agents 03 medical and health sciences Hepatitis B Chronic Ribonucleases Genome editing Transcription Activator-Like Effector Nucleases Medicine Clustered Regularly Interspaced Short Palindromic Repeats Hepatitis B Vaccines RNA Messenger 030304 developmental biology Hepatitis B virus Gene Editing 0303 health sciences Transcription activator-like effector nuclease Dose-Response Relationship Drug business.industry cccDNA Genetic Therapy Hepatitis B 021001 nanoscience & nanotechnology medicine.disease Virology Zinc finger nuclease Zinc Finger Nucleases Chronic infection Viral replication Nanoparticles 0210 nano-technology business |
| Zdroj: | Advanced drug delivery reviews. 168 |
| ISSN: | 1872-8294 |
| Popis: | Chronic infection with the hepatitis B virus (HBV) remains a significant worldwide medical problem. While diseases caused by HIV infection, tuberculosis and malaria are on the decline, new cases of chronic hepatitis B are on the rise. Because often fatal complications of cirrhosis and hepatocellular carcinoma are associated with chronic hepatitis B, the need for a cure is as urgent as ever. Currently licensed therapeutics fail to eradicate the virus and this is attributable to persistence of the viral replication intermediate comprising covalently closed circular DNA (cccDNA). Elimination or inactivation of the viral cccDNA is thus a goal of research aimed at hepatitis B cure. The ability to engineer nucleases that are capable of specific cleavage of a DNA sequence now provides the means to disable cccDNA permanently. The scientific literature is replete with many examples of using designer zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and RNA-guided endonucleases (RGENs) to inactivate HBV. However, important concerns about safety, dose control and efficient delivery need to be addressed before the technology is employed in a clinical setting. Use of in vitro transcribed mRNA to express therapeutic gene editors goes some way to overcoming these concerns. The labile nature of RNA limits off-target effects and enables dose control. Compatibility with hepatotropic non-viral vectors is convenient for the large scale preparation that will be required for advancing gene editing as a mode of curing chronic hepatitis B. |
| Databáze: | OpenAIRE |
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