YolTech and East China Normal University Publish Breakthrough Study on In Vivo Genome Editing for Blood Disorders

Shanghai, China – November 5, 2024 - YolTech’s co-founders, Dr. Yuxuan Wu, Dr. Zijun Wang, and Dr. Yuming Lu, in collaboration with East China Normal University, have published an original research article titled *In vivo genome editing of human hematopoietic stem cells for treatment of blood disorders by mRNA delivery on BioRxiv. The study demonstrates that through a novel lipid nanoparticle (LNP) system developed by YolTech, a single or repeated intravenous injection can effectively deliver base editor mRNA directly to bone marrow cells and hematopoietic stem cells (HSCs). This groundbreaking method enables precise editing of essential genes and significantly activates fetal hemoglobin production, revealing strong therapeutic potential for treating monogenic blood disorders such as β-thalassemia and sickle cell disease.

Genetic Basis and Treatment Strategy for β-Hemoglobinopathies

β-hemoglobinopathies, including β-thalassemia and sickle cell disease, are genetic blood disorders caused by mutations in the hemoglobin gene, leading to lifelong dependence on blood transfusions and iron chelation therapy. Studies suggest that activating fetal hemoglobin, which remains dormant in adults, can substitute for the deficient adult hemoglobin, greatly alleviating anemia symptoms. YolTech’s innovative mRNA-LNP delivery system directly targets the bone marrow microenvironment and HSCs, bypassing the complex manufacturing and myeloablative conditioning steps associated with traditional cell therapy and providing a promising new approach to gene therapy for blood disorders.

Study Highlights and Methodology

In this study, YolTech researchers identified a novel site within the HBG promoter region through a CRISPR-based screen. Base editing at this specific site effectively activates fetal hemoglobin. Using their proprietary LNPs to deliver mRNA-encoded base editors, YolTech achieved precise in vivo editing of this site, which notably improved the red blood cell phenotype in β-thalassemia models. Further tests confirmed that edited HSCs could successfully reconstitute hematopoiesis and produce red blood cells with high fetal hemoglobin levels upon secondary transplantation into immunodeficient mice, demonstrating effective editing of long-term hematopoietic stem cells (LT-HSCs) in the bone marrow. The team also optimized various cationic lipids to enable efficient, stable gene editing within HSCs with reduced doses and injection frequency, minimizing off-target effects on other tissues and organs.

Future Implications

This study reveals that LNP systems can effectively deliver mRNA and guide RNA directly to bone marrow cells, including HSCs, offering a new pathway for the high-efficiency in vivo editing required for gene therapy of blood disorders.

Dr. Yuxuan Wu, Dr. Zijun Wang, and Dr. Yuming Lu from YolTech are corresponding authors, with Xue Saijuan, a Ph.D. candidate at East China Normal University, and Professor Liang Dan from Anhui Medical University serving as co-first authors.

Publication Link

https://www.biorxiv.org/content/10.1101/2024.10.28.620445v1](https://www.biorxiv.org/content/10.1101/2024.10.28.620445v1

About YolTech

YolTech Therapeutics is a clinical-stage in vivo gene editing company committed to pioneering the next generation of precision genetic medicines. Our approach combines innovative gene editing technologies with an advanced lipid nanoparticle (LNP) delivery system, creating a versatile platform designed to address a wide range of serious diseases. Central to our mission is the development of internal capabilities, including end-to-end manufacturing, to ensure the highest standards of quality and scalability. Our lead candidate, targeting ATTR, marks a significant milestone as China’s first LNP-mediated in vivo gene editing therapy to enter clinical development. With promising early clinical outcomes, YolTech is also advancing therapies for familial hypercholesterolemia (FH) and primary hyperoxaluria type 1 (PH1). As a company dedicated to transforming the treatment landscape, YolTech continues to push the boundaries of what is possible in gene editing. For more information, please visit www.yoltx.com.