The advent of the CRISPR/Cas system for gene editing has revolutionised biomedicine; from preclinical research and animal models to clinical trials and what lies between.
Animal Models
Parrington outlined the potential for the application of gene editing in larger animal models. CRISPR/Cas has had a large impact on mouse models, making it easier and more economical to make a variety of transgenic animals like knock out, knock in, or conditional models like floxed mice.
Beyond mice, Parrington explained that larger animals like pigs or primates could also be used as models. He suggested that larger extractable blood volumes and the potential similarity to human biology, are both examples of why other models could be worthwhile.
However, the use of larger animal models also comes with problems. For example, larger animals require more space and resources to be kept which ends up inflating the cost of a project. Furthermore, there are longstanding ethical implications that have not been resolved when it comes to gene editing.
Clinical Applications
One of the most exciting applications of CRISPR/Cas has been in the clinic. Parrington noted the recently FDA-approved treatments for beta thalassemia as being examples of this. He commented that these therapies had the benefit of being ex vivo treatments, rather than the more difficult task of trying to modulate gene expression in vivo.
For other genetic disorders, which effect for example the brain, liver, or muscles, there is no way to remove the organ, modify it, and then implant it back into the body. For those diseases, the development of in vivo methods is crucial for therapy development. Parrington stressed that the largest challenge in this field is delivery, which has become an impetus for the development of many innovative delivery systems.
Ethics of Germline Gene Therapy
Parrington raises ethical concerns surrounding germline gene editing, emphasising the potential risks of off-target effects and the need for rigorous safety evaluations before clinical applications can be pursued. He acknowledges the ongoing debate regarding the implications of editing human embryos and the necessity for responsible research practices.
Agricultural Applications
Lastly, the presentation touches on the potential of CRISPR in diagnostics and agriculture. CRISPR-based diagnostics could revolutionise how diseases are detected, while agricultural applications include enhancing crop resilience and livestock health. Parrington concludes by stressing the importance of public engagement in discussions about the ethical implications and benefits of CRISPR technology.
