To genetically correct a disease-causing point mutation in human induced pluripotent stem cells (iPSCs) derived from a hemophilia B patient.
There are, however, possible future scenarios in which a modification made in a research context for example to correct a disease-causing genetic mutation could, if this were to become permissible, be used in a treatment that would result in the birth of a child.
The award passed over one of the highest-profile fields of research, the so-called CRISPR-Cas9 gene editing technology that earlier this year allowed U.S. scientists to alter genes in a human embryo to correct a disease-causing mutation.
Given their capacity to differentiate into any human cell type, these cell lines might be reprogrammed to correct a disease-causing genetic defect in any tissue or organ, in addition to offering a more clinically realistic model for testing new drugs and studying disease mechanisms.
The rationale is that infused cells can provide a targeted therapy to precisely correct a complex disease phenotype.
Wu et al. was one of the first groups to show that it was possible to correct a genetic disease in vivo when they rescued a cataract phenotype by correcting a mutated Crygc gene [ 65].
Recently, several studies have reported that BM cells transplantation can partially correct liver disease in a WD model [ 13, 14].
The most robust possible study design would be to do both: insert a disease mutation into a wild-type cell line – thereby testing for sufficiency of the mutation for disease – and correct the disease mutation in a patient-specific iPSC line – thereby testing for necessity of the mutation for disease (Liu et al., 2012; Reinhardt et al., 2013).
Here we delivered the human ACDase cDNA analogously to Asah1P361R/P361R mice in an initial attempt to correct their disease manifestations.
This means that treatment could be repeated after birth, if that was necessary to continue to correct the disease.
In summary, our preclinical results in mouse models of Fabry disease suggest that for α-galactosidase A null Fabry patients, SRT as a monotherapy is unlikely to correct disease symptoms effectively.
