We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs.
Transfection experiments demonstrated correction of the defect in mutant fibroblasts.
Finally, one embryo demonstrated correction of chromosome 15, which had the reciprocal polar body aneuploidy, but exhibited multiple monosomies due to errors presumably occurring after maternal meiosis.
Several groups have also demonstrated correction of genetic disease genes, such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene in intestinal organoids [ 54], a dominant mutation in the Crygc gene that causes cataracts [ 55], and the Duchenne muscular dystrophy (Dmd) gene in mouse zygotes [ 56].
The primary registration trials used for the approval of epoetin alfa demonstrated correction of anemia and virtual elimination of transfusions (>90% reduction) in patients treated with ESAs to a mean hemoglobin (Hb) of 11.7 g/dL (within the target range of 10.7 to 12.7 g/dL) [ 7].
To demonstrate phenotypic correction at the CYBB locus, as well as genotypic correction, the iPS cells were differentiated into monocytes using an embryoid body-based protocol developed in our laboratory [15,26].
Hence, active profiling and polishing can demonstrate a correction of the shape error of the surface to be machined.
Therefore, the current results demonstrate that correction for non-autocorrelation is indispensable for NIRS SPM analysis, whereas several previous studies [31, 46, 47] have not taken this point into consideration.
These results demonstrate that correction of the abnormal mineral ion homeostasis by feeding with a high-calcium rescue diet is effective to rescue the PDDR phenotype of 1α-OHase mutant mice.
The true virial coefficient can be obtained by extrapolation of Kc/R to vanishing value of K. Light scattering of a well characterized sample of polystyrene in cyclohexane at three different wavelengths and several temperatures has been used to demonstrate the correction for turbidity.
