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E. González-Romero et al.
and to ensure that epigenetic modification is heritable upon cell division.
Last but not least, the contribution of CRISPR/Cas9 to multiplex editing in CAR-T cells to create safer and more effective treatments cannot be underestimated, and it is highly likely that this technique will move forward the field of cancer immunotherapy for personalized T-cell- based therapies. The engineering of novel CAR-T cells by pharmaceutical industries, resulting in costly and unaf- fordable treatments for the general population, should be accompanied by their production by academia institu- tions, which could make it easier to tailor CAR-T cells for each patient. Thus, drug regulatory authorities should facilitate their academic production and provide resources for CAR-T- cell manufacturing processes, so that these can be simplified and automated to enable scaling up of these cell products.
Conclusions
CRISPR/Cas9 technology is a revolutionary approach for genome editing with wide applications in molecular biology, genetics, and medicine. It has great potential for dissecting gene function, modeling diseases and editing human genes for curative treatment. The number of pub- lications in this field has doubled every year since its intro- duction, and the CRISPR/Cas9 system is now more wide- ly used in biotechnology and research laboratories than
other, more time-consuming and expensive approaches such as zinc-finger nucleases or TALEN. In hematology, CRISPR/Cas9 can be used to model diseases using cul- tured cells or model organisms, but perhaps more impor- tantly, it can be a valuable approach to correct ex vivo mutations and chromosomal aberrations in cells from patients with blood disorders for autologous HSC trans- plantation. However, many pitfalls and challenges need to be overcome for the translation of CRISPR/Cas9 gene editing to the clinic. For example, we do not know the minimum number of edited cells needed to functionally correct a genetic defect or if gene editing can be applied to treat multigenic diseases. Further research is necessary to implement CRISPR/Cas9 in the clinical context, so that genome editing-based treatments are available to patients. In conclusion, the CRISPR/Cas9 revolution brings us a specific, efficient and versatile tool for editing genes. Nowadays, technology is no longer a limitation and scien- tists can probably do any genetic manipulation they can dream of.
Acknowledgments
This work was supported by Ayudas FEDER CIBERONC [CB16/12/00284], Instituto de Salud Carlos III [PI16/01113, PI17/00011, CP16/00011], Conselleria de Educación, Investigación, Cultura y Deporte [PROMETEOII/2015/008, ACIF/2018/255], MINECO [RYC-2015-17534, SAF2017- 82171-R], and Beca Leonardo a Investigadores y Creadores Culturales de la Fundación BBVA.
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