Progress and Criteria in Public Health Applications of Gene Therapy and Gene Editing: Beyond the White Paper

Abstract

Background: In 2023, the FDA approved two gene therapies for sickle cell disease (SCD), one of which follows a standard gene therapy protocol and the other a gene editing (CRISPR/Cas9) approach. Other gene therapy protocols for conditions relating to public health continue to advance and are being discussed in academic and professional circles. This review examines the pace of public health-related gene therapy and gene editing development since the publication of a key British white paper dealing with the pace of fruition in this field.

Summary: Gene therapy developments related to public health fit into three overarching baskets: (1) gene therapy and editing for rare, single-gene disorders (e.g., homozygous familial hypercholesterolemia and hereditary amyloidosis polyneuropathy); (2) gene therapy and editing for high prevalence conditions (e.g., SCD); and (3) genetic engineering and gene editing of mosquitoes transmitting tropical disease. While the protocols listed in this purposive inspection largely center around phase III (comparing treatments), with several in phase II (establishing efficacy) and phase I (assessing safety), costs of actual administration can span USD 2.1 to 3.1 million. By comparison, conventional SCD treatment runs between USD 22,500 and USD 200,000 per year for its most severe forms. Expert and public buy-in of gene editing of mosquitoes to reduce tropical disease and for human germline gene editing contain many caveats, with public health serving a useful monitoring and filtering role for how a technology might be deemed permissible.

Key messages: Gene therapy has advanced beyond the stage where possible consequences serve as an automatic barrier to mainstream use, moving it closer to British white paper objectives. Ethical and feasible adoption by public health, taking into account population needs, will most likely happen through a combination Medicaid and Medicare, as opposed to the system governing newborn screening, under arrangements similar to the Centers for Medicare and Medicaid Services' coverage under evidence development program. Vector gene drives to alleviate tropical disease should remain privately financed, with this type of financing also being used for the vast majority of gene therapies entering the market. Though the criteria for germline applications continue to evolve, in the end such applications do not serve public health purposes. Academic public health has a monitoring role to play as relevant gene therapy and gene editing trials evolve; public health practice a referral and field monitoring role in the T3 (implementation) and T4 (population outcomes) translational research phases for the few applications that could justifiably receive public funding and public health support.

Keywords: Access; Amyloidosis; CRISPR/Cas9; Clinical trials; Dengue fever; Ethics; Familial hypercholesterolemia; Gene editing; Gene therapy; Glycogen storage disease type Ia; Hemophilia; Public health policy; Public participation; Sickle cell disease.