From the current data it is hard to deduce whether AID implicates on CLL development by single mutagenic off-target events contributing to initial malignant transformation or whether AID implicates on clonal evolution of CLL by constantly mediating off-target DNA damage during disease progression.
All published studies have suggested that the CRISPR/Cas9 mediated off-target mutagenesis could vary depending on the sgRNA design and target sequence.
FGF23 itself has been shown to mediate off-target direct end-organ toxicity in the heart promoting cardiomyocyte hypertrophy.
We examined the role of carotenoids in mediating trade-offs between coloration, health maintenance and life history traits in a wild population of the Eurasian kestrel (Falco tinnunculus; hereafter kestrel).
It is beyond the scope of the present manuscript to determine the mechanistic basis of the reported phenotypes, but future characterization of isogenized strains from these populations could be leveraged to test of the role of AMPs in mediating trade-offs between resistance and pathogenicity.
To rule out the possibility that the effect of her8a morpholinos was mediated by off-targeted apoptosis, all her8a MOs were co-injected with a p53 MO and we did not observe any detectable deviation in Her8a morphants with or without p53 MO (Fig. S6).
However, it has been claimed that such effects are mediated by off-target interactions.
Next, we investigated whether the effects of SP600125 depend on the inhibition of MPS1 or are mediated by off-target mechanisms.
Treatment of cells with GSK2606414, a potent PERK inhibitor, provided a protective effect against IPA toxicity, providing further support for the model that IPA toxicity is mediated by off-target inhibition of PERK.
As SHM and CSR are both highly mutagenic events, AID was soon suspected to also mediate off-target DNA damage.
Immune activation influences both thermoregulation and shelter use, yet its role in mediating a trade-off between these two important processes is unclear.
