Genetic Engineering Publications - GEG Tech top picks

Clinicians treating patients with CAR T cells have become adept at identifying and treating acute neurotoxicity, a common adverse event associated with the therapy. Researchers at Mount Sinai published a case study in Nature Medicine of a patient who developed a neurocognitive, hypokinetic movement disorder with features of Parkinson's disease after receiving the CAR-T therapy targeting the B-cell maturation antigen (BCMA) called ciltacabtagene autoleucel in the CARTITUDE-1 clinical trial. Since reports of this toxicity have not been observed with CD19-directed CAR-T therapies for other blood cancers, it appears to be specifically associated with BCMA-directed CAR-T. As it turns out, Parekh and colleagues found that BCMA is expressed on certain brain cells, and they saw evidence that BCMA-targeted CAR-T cells entered the patient's cerebrospinal fluid and crossed the blood-brain barrier. With ciltacabtagene autoleucel poised to become the second BCMA-directed CAR-T to gain commercial approval later this year, clinicians should discuss the potential benefits and risks of the therapy with their patients. They also need to be vigilant about screening for late neurological toxicities until researchers can make improvements to the new CAR-T constructs to mitigate the risk. 

Here the authors developed a stable cell line expressing α-SYN endogenously tagged with NanoLuc luciferase reporter using CRISPR/Cas9-mediated genome editing. This allows efficient measurement of transcriptional activity of α-SYN in its native epigenetic landscape which is not achievable using exogenous transfection-based luciferase reporter assays. For the authors, this is the first report showing endogenous monitoring of α-SYN transcription, thus making it an efficient drug screening tool that can be used for therapeutic intervention in PD.