A nanomedicine comprising a guide RNA and an mRNA co-encapsulated in a lipid nanoparticle for delivery to hepatocytes holds promise for a functional cure for chronic hepatitis B through epigenetic sil...

The high error rate of the hepatitis B virus (HBV) polymerase leads to a genetically diverse quasispecies in individuals with chronic hepatitis B. Data regarding the propagation of these variants in individual hepatocytes may provide insight into viral replication and diversity of covalently closed circular DNA (cccDNA), which is the template for HBV replication.MethodsWe developed sequencing protocols to characterize HBV diversity between and within hepatocytes using RNA extracted from individually isolated hepatocytes. We sequenced HBV in >200 hepatocytes in 4 liver biopsies from people with HIV/HBV (HB1, HB2, HB3, HB6).ResultsWe found that 2 biopsies (HB1 and HB6) showed HBV diversity between hepatocytes that met an experimentally identified threshold. Specifically, in HB1, HBV sequences from 86 individual cells were from 2 different haplotypes of genotype D: 70.2% of cells with haplotype a, 5.8% with haplotype b, and 24% with both haplotypes in the same cell. Furthermore, within single hepatocytes, up to 3 different HBV sequences were present per cell, including some cells with both genotypes A and D. HB6, who received years of lamivudine monotherapy, had evidence of drug resistance mutations distributed among hepatocytes and demonstrated up to 3 different sequences, including wild-type and drug-resistant sequences, in the same hepatocyte. Modeling of infected hepatocytes did not reveal evidence of local HBV spread based on spatial proximity.ConclusionsTaken together, our findings demonstrate that individual hepatocytes may harbor multiple, transcriptionally active HBV cccDNA molecules, which likely arose from distinct infection events.

Occult HBV infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA (covalently closed circular DNA [cccDNA] and/or relaxed circular DNA [rcDNA]) in the l...

Occult HBV infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA (covalently closed circular DNA [cccDNA] and/or relaxed circular DNA [rcDNA]) in the l...

Precision BioSciences erzielt in der Hepatitis-B-Therapie einen klinischen Nachweis für die cccDNA-Reduktion. Die liquiden Mittel sichern die Studienfinanzierung bis 2028.

Precision BioSciences (Nasdaq: DTIL) reported Q2 2026 results and a business update, highlighting first clinical biopsy evidence from the Phase 1 ELIMINATE-B trial that PBGENE-HBV directly reduces hepatitis B cccDNA. A patient showed a 1-log reduction with <1% cccDNA remaining after two 0.4 mg/kg doses, and repeat dosing in another patient increased anti-cccDNA effect. pgRNA became durably undetectable in 100% of evaluable patients, with substantial S-antigen declines across all dose levels and no dose-limiting toxicities in 16 patients.PBGENE-DMD advanced with two active Phase 1/2 FUNCTION-DMD trial sites now recruiting, and initial safety data targeted for year-end 2026. Cash, cash equivalents and restricted cash were $112.4 million at June 30, 2026, which Precision expects to fund operations and PBGENE-HBV and PBGENE-DMD data milestones through 2028. Q2 2026 R&D expenses were $12.4 million, G&A $6.8 million, and net loss was $32.7 million, including $13.5 million of other expense driven primarily by non-cash warrant liability revaluation.

Клинические данные показали устранение и инактивацию cccDNA – резервуара вируса гепатита B – у пациентов. Результаты стали первым доказательством, что технология редактирования генома способна воздейс...

GSK’s “bepi” performs better than expected in efficacy trials, but its global impact is likely limited

Клиничните изследвания показаха елиминиране и инактивиране на cccDNA, резервоара на вируса на хепатит В, при пациентите. Резултатите са първото доказателство, че технологията за редактиране на генома може да се насочи директно към причинителя на хроничната инфекция. Това открива перспективата за пълно преодоляване на хепатита. Експерименталната генна терапия PBGENE-HBV е разработена от учени в Precision BioSciences. Терапията е насочена към отстраняване на cccDNA и едновременно инактивиране на вирусната ДНК в чернодробните клетки. Според компанията това е първият агент за генно редактиране, който първоначално е създаден специално за премахване на основния източник на репликация на вируса на хепатит В.

Reviewers: K Kim (Ajou University) | 📗📗📗📗◻️ • Y Xia & L Zhang (Wuhan University) | 📗📗📗📗◻️

Precision BioSciences (Nasdaq: DTIL) reported new ELIMINATE-B trial data for PBGENE-HBV in chronic hepatitis B at EASL 2026. Liver biopsies showed a 1-log (10-fold) reduction in cccDNA-derived transcripts after two 0.4 mg/kg doses, with indels inactivating polymerase in the remaining <1% of cccDNA.PBGENE-HBV achieved durable pgRNA loss in 100% of evaluable patients (n=6) and substantial HBsAg declines in all treated patients (n=15). Across 38 doses in 16 patients, no dose-limiting toxicities occurred; observed Grade 3 lab abnormalities and hypotension were reversible, with mitigation measures reducing severe events.

Precision BioSciences (NASDAQ: DTIL) will present late-breaking biopsy data for PBGENE-HBV at EASL Congress 2026, showing evidence of elimination and inactivation of cccDNA in liver biopsies from the ongoing Phase 1 ELIMINATE-B trial.The poster (LB26-51656 / LBP-043) will be presented by Man-Fung Yuen on May 27, 2026 at 8:30 CEST in Barcelona.