Breakthrough in Gene Therapy for NF1, a Bold Step Toward Targeting Tumors at Their Core

A team of investigators from the NTAP gene therapy replacement initiative published their groundbreaking gene replacement strategy for Neurofibromatosis type 1 (NF1) — one of the most common single-gene disorders worldwide.

Lead author, Dr. Renyuan Bai, and team paired a miniaturized version of the NF1 gene with a tailored adeno-associated virus (AAV) vector that targets NF1 tumor tissue with remarkable precision. Published in Nature Communications, the study not only shows a significant inhibition of tumor growth of aggressive NF1-driven cancers in preclinical models but also lays a strong foundation for the move to human trials.

This work combines expertise and support across medicine, biotechnology, and patient advocacy and research organizations like the Children’s Tumor Foundation and the Gilbert Family Foundation. It’s also a reminder of how bold, technically challenging barriers can inspire transformative solutions through meaningful collaboration.

“This study presents a viable path to gene replacement in NF1 tumors. By combining an optimized neurofibromin GRD payload with a tumor-tropic AAV, the NTAP team shows tumor targeting with anti-tumor activity in NF1 xenografts,” said Kalyan Vinnakota, Ph.D., Director of Curing NF at the Gilbert Family Foundation. “Our next focus is advancing the translational readiness needed to reach IND-enabling milestones that can allow moving this therapeutic concept closer to the clinic.”

Building on this momentum, the team is already looking ahead to understanding which NF1 tumor types stand to benefit most and how gene therapy might integrate with other treatment strategies. This next phase of research aims to refine delivery, improve precision, and expand the therapeutic potential for people living with NF1.

“This progress is crucial for achieving targeted delivery of the right payload to NF1 tumor cells,” added Elwy Okaz, Senior Scientific Program Manager for the Gene Therapy Initiative (GTI) at the Gilbert Family Foundation. “It will be exciting to further identify the NF1 tumor-cell subtypes most likely to benefit, and the combination therapies best positioned to modulate disease biology.”

The significance of this work extends far beyond the laboratory. For patients and families affected by NF1, each milestone in gene therapy represents not just scientific progress but renewed hope for effective, lasting treatments.

“For families living with NF, this research represents hope turned into action,” said Dr. Annette Bakker, CEO of the Children’s Tumor Foundation. “I want to warmly congratulate the NTAP team. The value of using the NF1 minigene approach, successfully packaged in an efficient vector represents an innovative novel treatment opportunity for our NF1 community.” Although important investments are still required to bring this modality to the patients, these findings are a crucial catalyzer for the next wave of gene and mRNA therapies.”

The AAV-NF vector lights a path toward gene-based therapies that target cancers at their genetic source, bringing renewed hope to individuals affected by NF1 and cancers like sarcoma and glioblastoma. The publication of this work also honors the vision and legacy of Dr. Verena Staedtke, whose leadership was instrumental in driving its success.

“This publication is a testament to Dr. Staedtke’s brilliance, vision, and dedication to bringing bold, transformative therapies to people with cancers caused by NF1 loss,” says Dr. Jaishri Blakeley . “The development of AAV-NF is a lasting part of her remarkable legacy.”

Explore Johns Hopkins Medicine Clinical Connections to see how this work is making an impact and read the full Nature Communications publication to learn more about the innovative science shaping the future of NF1 treatment.