Cellular and gene editing therapies, paired with a focus on global health, are transforming the narrative for monogenic diseases such as sickle cell disease and hemophilia. As a medical student in Africa, I vividly recall the monumental announcement of the completion of the Human Genome Project in 2003. This first-ever comprehensive mapping of more than 20,000 genes allowed for identification of germline mutations and set the stage for targeted therapies and advancement in gene editing therapies. More than 20 years later, it is incredible to witness the strides that the scientific community has made, and it is clear we are only at the cusp of the full potential of gene therapies.
The Scientific Program at this year’s ASH annual meeting will highlight these advances and more.
Therapeutic Gene Editing of Stem Cells in Classical and Malignant Hematology (Sunday, 9:30 a.m. - 11:05 a.m., CC, Room 29), will address the role of gene editing as a transformative tool in hematology. This session, sponsored by the Scientific Committee on Bone Marrow Failure and the Scientific Committee on Transplantation Biology & Cellular Therapies, will comprehensively explore gene editing applications, from basic science to clinical implementation. Paula Rio, PhD, has been tackling precision and efficiency by using a new gene editing approach — prime editing. She will discuss how it contrasts with clustered regularly interspaced short palindromic repeats (CRISPR) and lentiviral-based approaches, providing insight into “lab-to-bench” use of this approach for bone marrow failure disorders such as Fanconi anemia.
“Prime editing is a very precise strategy that allows the correction of different types of mutations, resulting in a healthy sequence, thus preserving the endogenous regulation of the gene,” Dr. Rio said. “Importantly, prime editing is potentially safer than the conventional CRISPR/Cas9 system, as the possibility of off-target effects is much lower.”
Justin Eyquem, PhD, will discuss the enhancement of chimeric antigen receptor T-cell functionality and manufacturing processes to expand the therapeutic potential in both classical and malignant hematology. In addition, Julia Skokowa, MD, PhD, will explore gene editing for severe congenital neutropenia and preleukemic syndromes. All these discussions will no doubt highlight innovative gene editing strategies and emerging priorities in cellular therapy.
Shifting Gears to Hemostasis
Paradigm Shifts in Hemostasis: From Mechanisms to Therapies and Back (Sunday, 4:30 p.m. - 5:45 p.m., CC, Room 28 A-D) will provide a comprehensive discussion of the advances in the science of hemostasis and the newest therapeutic strategies for bleeding and thrombotic disorders. “The evolution of treatment paradigms to prevent hemophilic bleeding over the past decade has been astounding and includes innovative aspects of joint health management by intensifying basic scientific studies to investigate the pathobiology of hemophilic arthropathy and new point-of-care imaging techniques to speed up interventions,” said Annette von Drygalski, MD, PharmD.
This session will unpack the recent developments in hemophilic joint pathobiology, pathophysiological mechanisms contributing to hemophilic arthropathy, and new imaging modalities like point-of-care (POC) ultrasound using the Joint Tissue Activity and Damage Examination POC musculoskeletal ultrasound protocol developed by Dr. von Drygalski and her group.
Daniël Verhoef, PhD, MSc, will also present research on the potential of a snake venom derivative to bypass factor Xa inhibitors. “Where traditional approaches have aimed to remove factor X-inhibiting [direct oral anticoagulants] from circulation, we are now simply bypassing these anticoagulants using a modified form of factor X that is not sensitive to these inhibitors,” Dr. Verhoef said. “This approach can have many benefits.” This presentation promises a compelling discussion of this new strategy, offering a promising strategy for patients requiring anticoagulation reversal while balancing prothrombotic risks.
Calling All Classical Blood Buffs
Today’s Ineffective Erythropoiesis: Insights into Molecular Mechanisms and Disease Pathophysiology (9:30 a.m. - 10:45 a.m., Manchester Grand Hyatt, Grand Hall D) offers a compelling lineup, including a discussion by Elizabeth S. Egan, MD, PhD, on how Plasmodium falciparum malaria disrupts erythropoiesis, contributing to anemia and multiorgan dysfunction. Dr. Egan will highlight emerging research on parasite reservoirs in erythroblastic islands and discuss single-cell analyses revealing the molecular interplay between P. falciparum and the hematopoietic niche. Crosstalk Between Iron Homeostasis and Metabolism (Monday, 4:30 p.m. - 5:45 p.m., CC, Room 29), will be a treat for those iron enthusiasts in attendance.
All of these Scientific Program sessions will showcase the transformative power of precision medicine in action. From prime editing to paradigm shifts in hemostasis, the innovations presented are not just rewriting the textbook — they’re rewriting the DNA of hematology itself.
