Vigorous efforts are being made to manipulate cellular functions in a desirable manner for biomedical purposes. Recent advances in platform technologies have made cell editing achievable; this includes generation of induced pluripotent stem cells and chimeric antigen receptor T cells, as well as direct cell reprogramming. mRNA, as compared to DNA, is an excellent tool for potentiating cell editing technologies, owing to its distinct properties in gene introduction. Herein, hepatocytes were edited ex vivo and in vivo, by introducing pro-survival mRNA, to be resistant to cell death. DNA-based introduction of pro-survival gene poses safety concerns due to its genomic integration, as prolonged and uncontrolled expression of pro-survival proteins after the integration may promote cancer. In contrast, mRNA lacks such a risk. Moreover, mRNA-based introduction of Bcl-2, a pro-survival factor, was more effective in preventing the death of cultured hepatocytes than Bcl-2 plasmid DNA (pDNA) introduction. Mechanistically, mRNA induced protein expression in a larger percentage of the hepatocytes compared to pDNA, presumably because the process of pDNA nuclear entry in transfection is challenging. In hepatocyte transplantation to mouse liver, ex vivo introduction of Bcl-2 mRNA significantly improved the engraftment efficiency of the hepatocytes, leading to successful functional support of the liver in a mouse model of chronic hepatitis. Furthermore, in vivo administration of Bcl-2 mRNA exhibited an anti-apoptotic effect on the hepatocytes of a mouse model of fulminant hepatitis. These results demonstrate the potential advantages of mRNA introduction over DNA introduction in cell editing.Remarkable progress in our ability to analyze diseased tissue has revolutionized our understanding of disease. From a simplistic understanding of abnormalities in bulk tissue, there is now increasing recognition that the heterogeneous and dynamically evolving disease microenvironment plays a crucial role in disease pathogenesis and progression as well as in the determination of therapeutic response. https://www.selleckchem.com/products/BEZ235.html The disease microenvironment consists of multiple cell types as well as the various factors that these cells secrete. There is now immense interest in treatment strategies that target or modify the abnormal disease microenvironment, and a deeper understanding of the mechanisms that drive the formation, maintenance, and progression of the disease microenvironment is thus necessary. The advent of 3-dimensional (3D) cell culture technology has made possible the reconstitution of the disease microenvironment to a previously unimaginable extent in vitro. As an intermediate between traditional in vitro models based on 2-dimensional (2D) cell culture and in vivo models, 3D models of disease enable the in vitro reconstitution of complex interactions within the disease microenvironment which were unamenable in 2D while simultaneously allowing the mechanistic analysis of these interactions that would be difficult to perform in vivo. This symposium review aims to highlight the promise of using 3D cell culture technology to model and analyze the disease microenvironment using pancreatic cancer as an example.Bioinspired polymeric biomaterials with excellent cytocompatibility have been designed in this study. 2-Methacryloyloxyehtyl phosphorylcholine (MPC) is a phospholipid polymer and an essential polymeric biomaterial, which has been used in various biomedical and pharmaceutical applications including implantable medical devices. Furthermore, it is a methacrylate monomer unit and can be copolymerized with other vinyl monomers via conventional radical polymerization. The water-solubility of MPC polymers depends on the molecular composition and molecular weight of the polymers. PMB is a water-soluble polymer copolymerized with hydrophobic n-butyl methacrylate, and can be used as a solubilizing agent for poorly soluble drugs. The phospholipid polymers showed low cytotoxicity, and the solubilized drugs effectively not only penetrated into the cells but also into the surrounding tissues. In addition, the water-soluble MPC polymer containing a phenylboronic acid moiety was observed to spontaneously form polymeric hydrogels with polyol compounds. The reversible polymer hydrogels were used as artificial extracellular matrices for cell immobilization and cell engineering. Polymeric biomaterials with intelligent interfaces might be explored as innovative techniques for application in pharmaceutical and life sciences.One of the current critical issues in nucleic acid delivery is the efficient mRNA delivery into target cells, directed toward clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) genome editing. To this end, we have developed a variety of cationic polyaspartamide derivatives with varying side chain structures because they can form nanocomplexes, termed polyplexes, with mRNA through electrostatic interactions. Interestingly, the delivery functions were highly affected by the chemical structures of the polyaspartamide side chains. Therefore, we review our previous research and provide a rationale for designing polypeptides for mRNA delivery.In "cell-function editing", the combination of biological methods with artificial methods is a promising way to effectively implement functions that live cells do not originally possess. In the present symposium review, two approaches with methodology of building "artificial organelle" were implemented for editing cellular functions. One approach is the "membrane-bound artificial organelle", which is mainly created from polymeric nanocapsules that function in cells, and the other approach mimics the "membraneless organelle", which has recently gained immense interest in the field of cell biology. Furthermore, some examples of artificial cells are also described, which were constructed by utilizing artificial organelles. In this context, some recent progress has been observed in the author's research on the development of polyion complex (PIC) materials, in particular, PICsome-based nanoreactors, designer coacervates for protein sequestration, and yolk-shell PIC structures that are reminiscent of artificial cells.