Gene-Editing and RNA Interference in Treating Hepatitis B: A Review

Abstract

The hepatitis B virus (HBV) continues to cause substantial health and economic burdens, and its target of elimination may not be reached in 2030 without further efforts in diagnostics, non-pharmaceutical prevention measures, vaccination, and treatment. Current therapeutic options in chronic HBV, based on interferons and/or nucleos(t)ide analogs, suppress the virus replication but do not eliminate the pathogen and suffer from several constraints. This paper reviews the progress on biotechnological approaches in functional and definitive HBV treatments, including gene-editing tools, i.e., zinc-finger proteins, transcription activator-like effector nucleases, and CRISPR/Cas9, as well as therapeutics based on RNA interference. The advantages and challenges of these approaches are also discussed. Although the safety and efficacy of gene-editing tools in HBV therapies are yet to be demonstrated, they show promise for the revitalization of a much-needed advance in the field and offer viral eradication. Particular hopes are related to CRISPR/Cas9; however, therapeutics employing this system are yet to enter the clinical testing phases. In contrast, a number of candidates based on RNA interference, intending to confer a functional cure, have already been introduced to human studies. However, larger and longer trials are required to assess their efficacy and safety. Considering that prevention is always superior to treatment, it is essential to pursue global efforts in HBV vaccination.

Hepatitis B in Pediatric Population: Observational Retrospective Study in Romania

“…The most recent data estimate that approximately 85% of children under 1 year-old have been vaccinated with three doses for HBV, but only 46% received a TBD [ 20 ]. Even though in theory this prevention approach is efficient, there are studies that describe regions in Africa where TBD vaccination is not enough, urging for peripartum antiviral prophylaxis [ 27 , 28 , 29 , 30 ]. Since 2020, Tenofovir prophylaxis has been added to the list of recommendations for pregnant HBsAg-positive women with high viraemia, starting from 28 week of gestation until at least after birth.…”

“…Since 2020, Tenofovir prophylaxis has been added to the list of recommendations for pregnant HBsAg-positive women with high viraemia, starting from 28 week of gestation until at least after birth. Even so, it is estimated that this approach is successfully applied in only 3% of cases [ 20 , 26 , 27 , 28 , 29 , 30 ].…”

Longterm Outcome of Therapeutic Vaccination with a Third Generation Pre-S/S HBV Vaccine (PreHevbrioR) of Chronically HBV Infected Patients

“…The cumulative experience from several studies highlights that NUC monotherapy significantly reduces HBV DNA but often fails to decrease HBsAg levels in chronic HBV (CHB) [3,14]. Thus, exploring new strategies for suppressing HBsAg production, such as treatment with iRNA (Interference RNA) compounds or nucleic acid polymers (NAPs), is warranted [26][27][28][29]. NAPs therapy has shown promise in two clinical studies, leading to a 2-7 log reduction of HBsAg concentration in 12 patients [30,31].…”

Prospects for Controlling Hepatitis B Globally

“…CRISPR-based systems use engineered RNA-guided Cas nucleases to generate site-specific insertion-deletion (indel) mutations. Their role as anti-HBV agents is eagerly being pursued [ 34 , 36 , 37 ].…”