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Sudipto Roy, Carol Wicking, Carsten Bergmann and colleagues report that mutations in DZIP1L cause autosomal recessive polycystic kidney disease (ARPKD). Through studies of mouse and zebrafish models of DZIP1L loss of function, the authors demonstrate that DZIP1L is required for proper function of the periciliary diffusion barrier.
While CRISPR-Cas9 is a powerful technology, it’s in vivo application can be limited by unwanted off-target editing events. Here the authors present SLiCES, a self-limiting Cas9 circuit to enhance editing by preventing residual nuclease activity.
Tumour-specific T cells can be expanded in vitro and adoptively transferred for therapy, but this strategy is limited by induction of short-lived T cell populations. Here the authors activate Notch signalling in cultured mouse or human T cells, resulting in the production of a long-lived stem cell memory T cell population that can fight tumours in mice.
The first large trial of a multimodal lifestyle intervention combined with a nutritional supplement for dementia prevention was unsuccessful and adds to conflicting evidence from similar studies. Whether lifestyle interventions are biologically ineffective or whether the lack of efficacy is due to methodological limitations remains to be determined.