Ionizable lipid nanoparticles for RAS protease delivery to inhibit cancer cell proliferation.

Mutations in RAS, a family of proteins found in all human cells, drive a third of cancers, including many pancreatic, colorectal, and lung cancers. However, there is a lack of clinical therapies that can effectively prevent RAS from causing tumor growth. Recently, a protease was engineered that specifically degrades active RAS, offering a promising new tool for treating these cancers. However, like many other intracellularly acting protein-based therapies, this protease requires a delivery vector to reach its site of action within the cell. In this study, we explored the incorporation of cationic lipids into ionizable lipid nanoparticles (LNPs) to develop a RAS protease delivery platform capable of inhibiting cancer cell proliferation in vitro and in vivo. A library of 13 LNPs encapsulating RAS protease was designed, and each formulation was evaluated for in vitro delivery efficiency and toxicity. A subset of four top-performing LNP formulations was identified and further evaluated for their impact on cancer cell proliferation in human colorectal cancer cells with mutated KRAS in vitro and in vivo, as well as their in vivo biodistribution and toxicity. In vivo, both the concentration of cationic lipid and type of cargo influenced LNP and cargo distribution. All lead candidate LNPs showed RAS protease functionality in vitro, and the top-performing formulation achieved effective intracellular RAS protease delivery in vivo, decreasing cancer cell proliferation in an in vivo xenograft model and significantly reducing tumor growth and size. Overall, this work demonstrates the use of LNPs as an effective delivery platform for RAS proteases, which could potentially be utilized for cancer therapies.

Care to Share? Patients in Private Rooms Are More Likely to Recommend a Hospital to Others.

A patient's likelihood to recommend a hospital is used to assess the quality of their experience. This study investigated whether room type influences patients' likelihood to recommend Stanford Health Care using Hospital Consumer Assessment of Healthcare Providers and Systems survey data from November 2018 to February 2021 (n = 10,703). The percentage of patients who gave the top response was calculated as a top box score, and the effects of room type, service line, and the COVID-19 pandemic were represented as odds ratios (ORs). Patients in private rooms were more likely to recommend than patients in semi-private rooms (aOR: 1.32; 95% CI: 1.16-1.51; 86% vs 79%, p < .001), and service lines with only private rooms had the greatest increases in odds of a top response. The new hospital had significantly higher top box scores than the original hospital (87% vs 84%, p < .001), indicating that room type and hospital environment impact patients' likelihood to recommend.

Delivery technologies for T cell gene editing: Applications in cancer immunotherapy.

While initial approaches to adoptive T cell therapy relied on the identification and expansion of rare tumour-reactive T cells, genetic engineering has transformed cancer immunotherapy by enabling the modification of primary T cells to increase their therapeutic potential. Specifically, gene editing technologies have been utilized to create T cell populations with improved responses to antigens, lower rates of exhaustion, and potential for use in allogeneic applications. In this review, we provide an overview of T cell therapy gene editing strategies and the delivery technologies utilized to genetically engineer T cells. We also discuss recent investigations and clinical trials that have utilized gene editing to enhance the efficacy of T cells and broaden the application of cancer immunotherapies.