An aptamer-mediated base editing platform for simultaneous knockin and multiple gene knockout for allogeneic CAR-T cells generation.

Gene editing technologies hold promise for enabling the next generation of adoptive cellular therapies. In conventional gene editing platforms that rely on nuclease activity, such as clustered regularly interspaced short palindromic repeats CRISPR-associated protein 9 (CRISPR-Cas9), allow efficient introduction of genetic modifications; however, these modifications occur via the generation of DNA double-strand breaks (DSBs) and can lead to unwanted genomic alterations and genotoxicity. Here, we apply a novel modular RNA aptamer-mediated Pin-point base editing platform to simultaneously introduce multiple gene knockouts and site-specific integration of a transgene in human primary T cells.

Developing an intrasalivary gland botox service for patients receiving long-term non-invasive ventilation at home: a single-centre experience.

Introduction: Sialorrhoea is a debilitating symptom in neurological disease and there is a growing literature for the use of intrasalivary gland Botulinum Toxin (botox) injections in its management. However, provision of intrasalivary gland botox remains inconsistent and sialorrhoea is often poorly controlled in motor neuron disease (MND).Sialorrhoea in association with bulbar dysfunction can cause intolerance of non-invasive ventilation (NIV) and respiratory infection, so its treatment is critical within a home ventilation service (HVS).

Kanglemycin A Can Overcome Rifamycin Resistance Caused by ADP-Ribosylation by Arr Protein.

Rifamycins, such as rifampicin (Rif), are potent inhibitors of bacterial RNA polymerase (RNAP) and are widely used antibiotics. Rifamycin resistance is usually associated with mutations in RNAP that preclude rifamycin binding. However, some bacteria have a type of ADP-ribosyl transferases, Arr, which ADP-ribosylate rifamycin molecules, thus inactivating their antimicrobial activity.

Immunotherapy to get on point with base editing.

Engineered immune cell therapy is revolutionising the field of cancer therapeutics. US Food and Drug Administration (FDA) approval of two chimeric antigen receptor (CAR)-T cell products for the treatment of haematological malignancies paved the way for individualised cancer treatment. However, multiple genetic edits will be required to improve the efficacy of CAR-T cell therapies if they are to treat refractory malignancies successfully, particularly solid tumours.