TY - JOUR TI - NanoScript DO - https://doi.org/doi:10.7282/T38054M6 PY - 2015 AB - Stem cell engineering for regenerative medicine offers new hope for treating many ailments and injuries. Hence, there is an urgent demand by stem cell scientists for an alternative platform that induces stem cell differentiation in a safe and efficient manner. Stem cell differentiation is inherently regulated by transcription factors (TFs), which are multi-domain proteins that interact with DNA to control expression of target genes, and thus, TFs are master regulators of gene expression and cellular behavior. Recently, scientists have developed synthetic transcription factors (STFs), which are small molecules that mimic the function of the individual domains on TF proteins. This work presents the development a novel bio-inspired platform called NanoScript, which is an alternative approach for safe stem cell differentiation. NanoScript is a nanoparticle-based artificial TF protein because it is designed to replicate the function and structure of natural TF proteins. NanoScript was constructed by assembling STFs onto multifunctional nanoparticles. We first demonstrate that NanoScript localizes within the nucleus of cells, initiates transcription of a reporter plasmid by over 15-fold in cancer cells, and transcribes endogenous genes. The tunable and interchangeable components of NanoScript can easily be modified to either activate or deactivate any gene of interest. As a result, NanoScript was then demonstrated for three stem cell-based applications: 1) NanoScript targets myogenic genes to differentiate adipose-derived mesenchymal stem cells (ADMSCs) into muscle cells, 2) NanoScript modified with an epigenetic modulator, CTB, increases transcriptional potency and enhances differentiation of ADMACs into chondrocytes, and 3) NanoScript redesigned with gene repression molecules acts a transcriptional repressor protein because it downregulates gene expression to induce differentiation of neural stem cells into functional neurons. Because of its robust tunability and biocompatibility, the patented NanoScript platform is a promising alternative tool for research scientists for applications involving gene manipulation such as stem cell differentiation, cancer therapy, and cellular reprogramming. Moreover, the ability of NanoScript to induce stem cell differentiation in a non-viral and footprint-free manner is highly desired by stem cell clinicians, and hence, holds potential for use in stem cell-based therapies. KW - Chemistry and Chemical Biology KW - Nanoparticles KW - Stem cells KW - Transcription factors LA - eng ER -