July 17 Preclinical Quick Takes: Using CRISPR to edit TCRs, plus AAVs with synthetic promoters and AI for cancer diagnosis

CRISPR can modify TCRs to reprogram T cells
A Technical University Munich and Juno Therapeutics Inc. team led by TUM professor Dirk Busch used CRISPR to modify T cell receptors and create engineered T cells. As reported in a Nature Biomedical Engineering paper, T cells with the endogenous TCR loci removed via CRISPR and insertion of viral or tumor-specific TCRs showed transgenic TCR surface expression and responded to antigen-specific stimulation in vitro. Busch is a co-founder of Stage Cell Therapeutics GmbH, which Juno (now part of Celgene Corp.) acquired in 2015.

AAVs with synthetic promoters target different neuronal cell types
Researchers at Institute of Molecular and Clinical Ophthalmology Basel developed a library of 230 adeno-associated viruses, each with a different synthetic promoter, that can target neuronal and glial cell types and induce transgene expression, expanding the toolbox for specific cell-type gene therapies. Cell-type targeting of the AAVs to mouse and non-human primate retinas in vivo and human retinas ex vivo was described in a Nature Neuroscience study...