Mutation-Specific Gene Editing for Blood Disorders

Hundreds of inherited blood disorders have been characterized, which in their majority are still without effective palliative treatments. Although many of them are, in principle, curable by allogeneic hematopoietic stem cell transplantation, limited availability of compatible donors and persistent associated risks of treatment-related morbidity and mortality have prompted the search for alternative cures. As a result, gene therapy treatments have been developed, and for some of the more prominent blood disorders have reached the clinic and even market approval. Here, the most advanced approaches are based on gene addition by integrating viral vectors, which poses the inherent risk of insertional mutagenesis, or on disruption of disease modifiers by gene editing tools, which presupposes a fundamental understanding of disease pathology that for many blood disorders is still absent. For most inherited defects, mutation-specific editing would represent the most direct curative approach, solely based on the knowledge of underlying causative mutations. Driven by the rapid and ongoing development of gene editing tools, protocols and applications, editing technology is fast approaching such efficiency, accuracy and ubiquity, that clinically relevant mutation-specific applications for many diseases are within reach.

In this Research Topic, we will feature the latest findings and insights for editing-based mutation-specific therapy of blood disorders. Studies and reviews covering, among others, specific applications, new technology development, optimization of clinically relevant protocols, and translational and business aspects of mutation-specific therapies are welcome.

We encourage the submission of articles in the forms of Original Research, Reviews, and Hypothesis and Theory. Within the framework of mutation-specific editing for blood disorders, suitable sub-topics include, but are not limited to:

• Editing based on dsDNA endonuclease activity, nickase activity or chemical modification of intact DNA
• Recruitment or delivery of editing co-factors
• Optimization of on-target efficiency and precise on-target modification
• Editing of compound heterozygous conditions
• Reducing cost, reagent requirements and culture time
• Analysis of financial and business aspects, including patient numbers and competing therapies
• Comparison of universal and mutation-specific approaches
• Development of and application in mutation-specific animal models
• Novel approaches and optimization of in vivo and in vitro delivery


Dr. Miccio holds patents related to viral gene delivery vectors.
The Topic Editors acknowledge the use of image material from kindpng.com and from Crystal and Annie Spratt on unsplash.com.