Molecular therapy : the journal of the American Society of Gene TherapySep 7, 2025

A gene-engineered B cell treatment that maintains steady active factor IX levels for hemophilia B

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

BE-101 engineered B cells produced sustained active FIX-Padua in preclinical hemophilia B models and could be redosed.

Evidence

A preclinical engineered-cell study used CRISPR-Cas9 insertion of FIX-Padua into autologous B-lineage cells and found mouse FIX-Padua production within 1 day, steady state within 2 weeks, persistence beyond 184 days, near-linear redose response, and no off-target issues of concern in genotoxicity analyses.

Caveat

Durability, redosing, and safety are supported by animal tolerability and GLP toxicology studies, not by human hemophilia B outcomes.

Simplified

Hemophilia B gene therapy treatments have not addressed the need for predictable, durable, active, and redosable factor IX (FIX). Unlike conventional gene therapy, engineered B cell medicines (BCMs) are durable, redosable, and titratable and thus have the potential to address significant unmet needs in the hemophilia B treatment paradigm. BE-101 is an autologous BCM comprising expanded and differentiated B lymphocyte lineage cells genetically engineered ex vivo to secrete factor IX (FIX)-Padua. CRISPR-Cas9-mediated gene editing at the C-C chemokine receptor type 5 (CCR5) locus was used to facilitate transgene insertion of an adeno-associated virus 6-encoded DNA template via homology-directed repair. Transgene insertion did not alter B cell biology, viability, or differentiation into plasma cells. Appreciable levels of BE-101-derived FIX-Padua were detected within 1 day after IV administration in mice, and steady state was reached within 2 weeks and persisted for over 184 days. Redosing produced an increase in FIX-Padua production close to linear dose proportionality. Comprehensive genotoxicity analysis found no off-target issues of concern. No safety signals were observed in animal tolerability and Good Laboratory Practice toxicology studies. In conclusion, BE-101 produces sustained levels of active FIX-Padua with the ability to engraft without host preconditioning and with the potential for redosing and titratability.