CRISPR and Chromothripsis: Proceed with Caution

A Field Day for Gene-Edited Brassicas and Crop Improvement

“…4 The ECJ ruling of July 25, 2018, trumped the earlier U.K. ruling as to the status of gene editing, meaning that these edited Camelina metaphorically transformed into GM plants overnight. 5 Thus, Neequaye and colleagues would need to apply for ''Ministerial consent'' to grow their edited B. oleracea plants in the field, since they were now considered to be GM. This was even though the authors clearly demonstrated that the transgene carrying the Cas9, gRNAs, and selectable marker was absent from their plants.…”

“…2 To date, most efforts have focused on spurious editing at unintended sites in the genome. A wealth of literature is dedicated to identifying 3,4 and mitigating [5][6][7][8][9][10] these off-target edits. Recent observations have extended spurious editing events to the target site itself, 11 again prompting careful examination of editing outcome.…”

Generation of Allogeneic CAR T Cells through Specific Degradation of the T Cell Antigen Receptor by E3 Ubiquitin Ligase Fusion Proteins

“…For example, genetic ablation by gene-editing technologies such as CRISPR-Cas9 , and TALENs have similar functions as RNA interference (RNAi) . However, it has recently been reported that an on-target consequence of Cas9 genome editing is chromothripsis, which can lead to genomic instability and cancer. , Likewise, chronic expression of siRNAs can lead to pathway subversion via the upregulation of compensatory mechanisms, resulting in the loss of the desired knockout phenotype. , There is thus a need to develop alternative technologies capable of regulating protein expression. Proteolysis Targeting Chimeras (ProTACs) have been used to recruit E3 ligases to proteins of interest, resulting in their ubiquitination and degradation. , Similarly, LyTACs , have been used to cross-link target proteins to receptors that are trafficked to the lysosome, resulting in degradation of the attached cargo protein via endogenous cellular pathways.…”