Magnetic Nanoparticle-Assisted Non-Viral CRISPR-Cas9 for Enhanced Genome Editing to Treat Rett Syndrome.

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates.

Physician perceptions of drug utilization management: Results of a national survey.

The use of drug utilization management techniques such as formulary exclusions, prior authorizations, and step edits has risen sharply during the last decade, contributing to the growing burden on physicians and patients. Limited quantitative data exist, however, on physician perceptions of drug utilization management. A national survey was conducted between February 9 and March 30, 2021, targeting office-based physicians working in the United States to assess their perceptions on drug utilization management in their practice.

Out-of-Pocket Costs and Prescription Filling Behavior of Commercially Insured Individuals With Chronic Obstructive Pulmonary Disease.

This cohort study uses a longitudinal access and adjudication data set to evaluate prescription out-of-pocket costs and filling behaviors of commercially insured individuals with chronic obstructive pulmonary disease (COPD).

The Physician and Administrator-Reported Cost of Drug Utilization Management to Physician Practices: A Cross-Sectional Survey.

Background: The use of drug utilization management techniques such as formulary exclusions, prior authorizations, and step edits has risen sharply during the last decade, contributing to growing administrative costs for physician practices. However, limited data exist on the extent of these administrative costs, with previous studies relying on data from over a decade ago.

Objective: The aim of this study was to assess physician and practice administrator experiences with drug utilization management.

Quantifying The Economic Burden Of Drug Utilization Management On Payers, Manufacturers, Physicians, And Patients.

The continuing launch of innovative but high-price drugs has intensified efforts by payers to manage use and spending and by pharmaceutical manufacturers to support patient access and sales. Payers are restricting drug formularies, requiring more stringent prior authorizations, and raising patient cost-sharing requirements. Manufacturers are investing in programs that help patients and physician practices navigate administrative controls and help patients meet cost-sharing obligations.

Hybrid Graphene-Gold Nanoparticle-based Nucleic Acid Conjugates for Cancer-Specific Multimodal Imaging and Combined Therapeutics.

Nanoparticle-based nucleic acid conjugates (NP-NACs) hold great promise for theragnostic (diagnostic and therapeutic) applications. However, several limitations have hindered the realization of their full potential in the clinical treatment of cancer and other diseases. In diagnosis, NP-NACs, combined with conventional optical sensing systems, have been applied for cancer detection , but low signal-to-noise ratios limit their broad applications.

Overcoming Chemoresistance in Cancer via Combined MicroRNA Therapeutics with Anticancer Drugs Using Multifunctional Magnetic Core-Shell Nanoparticles.

In this study, we report the use of a multifunctional magnetic core-shell nanoparticle (MCNP), composed of a highly magnetic zinc-doped iron oxide (ZnFeO) core nanoparticle and a biocompatible mesoporous silica (mSi) shell, for the simultaneous delivery of let-7a microRNA (miRNA) and anticancer drugs (e.g., doxorubicin) to overcome chemoresistance in breast cancer.

Stem cell-based gene therapy activated using magnetic hyperthermia to enhance the treatment of cancer.

Stem cell-based gene therapies, wherein stem cells are genetically engineered to express therapeutic molecules, have shown tremendous potential for cancer applications owing to their innate ability to home to tumors. However, traditional stem cell-based gene therapies are hampered by our current inability to control when the therapeutic genes are actually turned on, thereby resulting in detrimental side effects. Here, we report the novel application of magnetic core-shell nanoparticles for the dual purpose of delivering and activating a heat-inducible gene vector that encodes TNF-related apoptosis-inducing ligand (TRAIL) in adipose-derived mesenchymal stem cells (AD-MSCs).

Large-Scale Nanoelectrode Arrays to Monitor the Dopaminergic Differentiation of Human Neural Stem Cells.

A novel cell-based biosensing platform is developed using a combination of sequential laser interference lithography and electrochemical deposition methods. This enables the sensitive discrimination of dopaminergic cells from other types of neural cells in a completely nondestructive manner. This platform and detection strategy may become an effective noninvasive in situ monitoring tool that can be used to determine stem cell fate for various regenerative applications.

Induction of stem-cell-derived functional neurons by NanoScript-based gene repression.

Even though gene repression is a powerful approach to exogenously regulate cellular behavior, developing a platform to effectively repress targeted genes, especially for stem-cell applications, remains elusive. Herein, we introduce a nanomaterial-based platform that is capable of mimicking the function of transcription repressor proteins to downregulate gene expression at the transcriptional level for enhancing stem-cell differentiation. We developed the "NanoScript" platform by integrating multiple gene repression molecules with a nanoparticle.

Inducing Stem Cell Myogenesis Using NanoScript.

Transcription factors (TFs) are multidomain proteins that play a critical role in orchestrating stem cell differentiation, but several limitations hinder the full potential of TF-based gene regulation. Here we report a unique strategy to emulate TFs and differentiate stem cells in a nonviral approach using an artificial, nanoparticle-based transcription factor called NanoScript. The NanoScript platform consists of a gold nanoparticle functionalized with small molecules that mimic the various domains of TFs.

Controlling differentiation of adipose-derived stem cells using combinatorial graphene hybrid-pattern arrays.

Control of stem cell fate by modulating biophysical cues (e.g., micropatterns, nanopatterns, elasticity and porosity of the substrates) has emerged as an attractive approach in stem cell-based research.

Integrating epigenetic modulators into NanoScript for enhanced chondrogenesis of stem cells.

N-(4-Chloro-3-(trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB) is a small molecule that functions by altering the chromatin architecture to modulate gene expression. We report a new CTB derivative with increased solubility and demonstrate CTB's functionality by conjugating it on the recently established NanoScript platform to enhance gene expression and induce stem cell differentiation. NanoScript is a nanoparticle-based artificial transcription factor that emulates the structure and function of transcription factor proteins (TFs) to effectively regulate endogenous gene expression.

Engineering Stem Cells for Biomedical Applications.

Stem cells are characterized by a number of useful properties, including their ability to migrate, differentiate, and secrete a variety of therapeutic molecules such as immunomodulatory factors. As such, numerous pre-clinical and clinical studies have utilized stem cell-based therapies and demonstrated their tremendous potential for the treatment of various human diseases and disorders. Recently, efforts have focused on engineering stem cells in order to further enhance their innate abilities as well as to confer them with new functionalities, which can then be used in various biomedical applications.

NanoScript: a nanoparticle-based artificial transcription factor for effective gene regulation.

Transcription factor (TF) proteins are master regulators of transcriptional activity and gene expression. TF-based gene regulation is a promising approach for many biological applications; however, several limitations hinder the full potential of TFs. Herein, we developed an artificial, nanoparticle-based transcription factor, termed NanoScript, which is designed to mimic the structure and function of TFs.

Combined magnetic nanoparticle-based microRNA and hyperthermia therapy to enhance apoptosis in brain cancer cells.

A novel therapy is demonstrated utilizing magnetic nanoparticles for the dual purpose of delivering microRNA and inducing magnetic hyperthermia. In particular, the combination of lethal-7a microRNA (let-7a), which targets a number of the survival pathways that typically limit the effectiveness of hyperthermia, with magnetic hyperthermia greatly enhances apoptosis in brain cancer cells.

Prospects for graphene-nanoparticle-based hybrid sensors.

Graphene is a single-atom thick, two-dimensional sheet of carbon that is characterized by exceptional chemical, electrical, material, optical, and physical properties. As a result, graphene and related materials, such as graphene oxide and reduced graphene oxide, have been brought to the forefront in the field of sensing. Recently, a number of reports have demonstrated that graphene-nanoparticle hybrid structures can act synergistically to offer a number of unique physicochemical properties that are desirable and advantageous for sensing applications.

Axonal alignment and enhanced neuronal differentiation of neural stem cells on graphene-nanoparticle hybrid structures.

Human neural stem cells (hNSCs) cultured on graphene-nanoparticle hybrid structures show a unique behavior wherein the axons from the differentiating hNSCs show enhanced growth and alignment. We show that the axonal alignment is primarily due to the presence of graphene and the underlying nanoparticle monolayer causes enhanced neuronal differentiation of the hNSCs, thus having great implications of these hybrid-nanostructures for neuro-regenerative medicine.

Nanotopography-mediated reverse uptake for siRNA delivery into neural stem cells to enhance neuronal differentiation.

RNA interference (RNAi) for controlling gene expression levels using siRNA or miRNA is emerging as an important tool in stem cell biology. However, the conventional methods used to deliver siRNA into stem cells result in significant cytotoxicity and undesirable side-effects. To this end, we have developed a nanotopography-mediated reverse uptake (NanoRU) delivery platform to demonstrate a simple and efficient technique for delivering siRNA into neural stem cells (NSCs).

Label-free polypeptide-based enzyme detection using a graphene-nanoparticle hybrid sensor.

A graphene-nanoparticle (NP) hybrid biosensor that utilizes an electrical hysteresis change to detect the enzymatic activity and concentration of Carboxypeptidase B was developed. The results indicate that the novel graphene-NP hybrid biosensor, utilizing electrical hysteresis, has the ability to detect concentrations of targeted enzyme on the micromolar scale. Furthermore, to the knowledge of the authors, this is the first demonstration of a graphene-based biosensor that utilizes a hysteresis change resulting from metallic NPs assembled on a graphene surface.