FDA Regulation of Clinical Applications of CRISPR-CAS Gene-Editing Technology.

Scientists have repurposed an adaptive immune system of single cell organisms to create a new type of gene-editing tool: CRISPR (clustered regularly interspaced short palindromic repeats)-Cas technology. Scientists in China have reported its use in the genome modification of non-viable human embryos. This has ignited a spirited debate about the moral, ethical, scientific, and social implications of human germline genome engineering. There have also been calls for regulations; however, FDA has yet to formally announce its oversight of clinical applications of CRISPR-Cas systems. This paper reviews FDA regulation of previously controversial biotechnology breakthroughs, recombinant DNA and human cloning. It then shows that FDA is well positioned to regulate CRISPR-Cas clinical applications, due to its legislative mandates, its existing regulatory frameworks for gene therapies and assisted reproductive technologies, and other considerations.

Enhancement of plasmid DNA immunogenicity with linear polyethylenimine.

The utility of plasmid DNA as an immunogen has been limited by its weak immunogenicity. In the present study, we evaluated the ability of a family of linear polyethylenimine (PEI) polymers, complexed to plasmid DNA, to augment DNA expression in vivo and to enhance antigen-specific adaptive immune responses. We showed that four of five structurally different PEIs that we evaluated increased in vivo DNA expression 20- to 400-fold, and enhanced DNA-induced epitope-specific CD8⁺ T-cell responses 10- to 25-fold in BALB/c and C57BL/6J mice respectively, when delivered intravenously. Functional studies of the PEI-DNA-induced CD8⁺ T-cell responses demonstrated that formulation of DNA with PEI was associated with increased numbers of cells secreting type I cytokines. In addition, PEI-DNA complexes improved antigen-specific T(H) 1-helper cell and humoral responses. Most importantly, the PEI-DNA complexes elicited memory cellular responses, capable of rapid expansion and accelerated clearance of a lethal dose of recombinant Listeria monocytogenes. Lastly, we identified physical properties of PEI-DNA complexes that are associated with enhanced DNA-elicited immunogenicity. These findings demonstrate that PEI polymers can play an important role in the development of DNA-based vaccines in the setting of infectious disease prevention and cancer therapy.