Progress on RNAi-based molecular medicines.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen J
PROVIDER: S-EPMC3418169 | biostudies-other | 2012
REPOSITORIES: biostudies-other
Publications
Progress on RNAi-based molecular medicines.
International journal of nanomedicine 20120726
RNA interference (RNAi) is a promising strategy to suppress the expression of disease-relevant genes and induce post-transcriptional gene silencing. Their simplicity and stability endow RNAi with great advantages in molecular medicine. Several RNAi-based drugs are in various stages of clinical investigation. This review summarizes the ongoing research endeavors on RNAi in molecular medicine, delivery systems for RNAi-based drugs, and a compendium of RNAi drugs in different stages of clinical dev ...[more]
Similar Datasets
Project description:RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery systems. Inspired by the immense progress with nanotechnology in drug delivery, efforts have been dedicated to the development of nanoparticle-based RNAi delivery systems. For example, a precisely engineered, multifunctional nanocarrier with combined passive and active targeting capabilities may address the delivery challenges for the widespread use of RNAi as a therapy. Therefore, in this review, we introduce the major hurdles in achieving efficient RNAi delivery and discuss the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics. In particular, some representative examples of nanoparticle-based delivery formulations for targeted RNAi therapeutics are highlighted.
| S-EPMC3649006 | biostudies-literature
Project description:RNAi-based therapy holds great promise, as it can be utilized for the treatment of multiple conditions in an accurate manner via sequence-specific manipulation of gene expression. To date, RNAi therapeutics have advanced into clinical trials for liver diseases and solid tumors; however, delivery of RNAi to leukocytes in general and to lymphocytes in particular remains a challenge. Lymphocytes are notoriously hard to transduce with RNAi payloads and are disseminated throughout the body, often located in deep tissues; therefore, developing an efficient systemic delivery system directed to lymphocytes is not a trivial task. Successful manipulation of lymphocyte function with RNAi possesses immense therapeutic potential, as it will enable researchers to resolve lymphocyte-implicated diseases such as inflammation, autoimmunity, transplant rejection, viral infections, and blood cancers. This potential has propelled the development of novel targeted delivery systems relying on the accumulating research knowledge from multiple disciplines, including materials science and engineering, immunology, and genetics. Here, we will discuss the recent progress in non-viral delivery strategies of RNAi payloads to lymphocytes. Special emphasis will be made on the challenges and potential opportunities in manipulating lymphocyte function with RNAi. These approaches might ultimately become a novel therapeutic modality to treat leukocyte-related diseases.
| S-EPMC5498814 | biostudies-literature
Project description:The Innovative Medicines Initiative is a public-private partnership between the European Union and the pharmaceuticals industry that was established in 2008, with an overall budget of €5.3 billion from 2008 until 2024. The objective of the initiative is to boost pharmaceutical innovation in Europe and speed up the development of innovative medicines, vaccines and medical technologies, in particular in areas with high unmet needs. This article discusses the objectives of the initiative, its governance and main results and impact. The initiative has proved to be a unique platform for multi-stakeholder collaborations across Europe. It has contributed to the acceleration of the development process for medicines, from drug discovery to clinical development. The initiative has made important steps towards accessing and using real-world evidence for pharmaceutical research and development, and for healthcare decision-making. Several projects have contributed to a better understanding of the causes of diseases, and some are already delivering results, such as a vaccine against Ebola virus. The initiative has also significantly contributed to building capacity and resources for open use by the broader research and innovation community.
| S-EPMC6105180 | biostudies-literature
Project description:Helicases are ubiquitous motor proteins that separate and/or rearrange nucleic acid duplexes in reactions fueled by adenosine triphosphate (ATP) hydrolysis. Helicases encoded by bacteria, viruses, and human cells are widely studied targets for new antiviral, antibiotic, and anticancer drugs. This review summarizes the biochemistry of frequently targeted helicases. These proteins include viral enzymes from herpes simplex virus, papillomaviruses, polyomaviruses, coronaviruses, the hepatitis C virus, and various flaviviruses. Bacterial targets examined include DnaB-like and RecBCD-like helicases. The human DEAD-box protein DDX3 is the cellular antiviral target discussed, and cellular anticancer drug targets discussed are the human RecQ-like helicases and eIF4A. We also review assays used for helicase inhibitor discovery and the most promising and common helicase inhibitor chemotypes, such as nucleotide analogues, polyphenyls, metal ion chelators, flavones, polycyclic aromatic polymers, coumarins, and various DNA binding pharmacophores. Also discussed are common complications encountered while searching for potent helicase inhibitors and possible solutions for these problems.
| S-EPMC4427233 | biostudies-literature
Project description:Substantial developments have occurred in the past 5-10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAF(V600E) mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine.
| S-EPMC3931461 | biostudies-literature
Project description:Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.
| S-EPMC2860122 | biostudies-literature
Project description:ObjectiveTo assess changes in medicine availability and prices as well as subsequent affordability during the early years of the National Essential Medicine System (NEMS) reform in China.MethodsData were obtained from four provinces through a field survey conducted in 2010-2011. Outcome measures were percentage availability, delivery efficiency, ratios of local prices to international reference prices (MPRs), and number of days' household income needed to purchase medicines. Prices were adjusted for inflation/deflation and purchasing power parity.ResultsUnder NEMS, the median MPR for essential medicines decreased from 3.27 times to 1.59 times from 2009 to 2010. The median medicine expenditure under standard treatments in 2010 equaled 1.06 days household income at a low-income level and 0.25 days household income at a middle-income level. A 25.67% reduction was observed in the average number of medicines stocked by primary healthcare facilities in 2011 compared with 2009 and the availability of essential medicines was 66.83%. During 2009-2011, suppliers could respond to 98.24% of the purchasing orders raised by primary healthcare facilities, and 89.32% of the order amounts could be delivered.ConclusionsThe market prices of essential medicines greatly decreased in China after the establishment of NEMS and showed improved affordability in the short term. However, current medicine prices remain high compared to international reference prices. Medicines were often unaffordable for economically backward residents. Future policies still need to target medicine availability as well as affordability.
| S-EPMC6072036 | biostudies-literature
Project description:ObjectivesChallenges remain in ensuring universal access to affordable essential medicines. We previously estimated the expected generic prices based on cost of production for medicines in solid oral formulations (ie, capsules or tablets) on the WHO Model List of Essential Medicines (EML). The objectives of this analysis were to estimate cost-based prices for injectable medicines on the EML and to compare these to lowest current prices in England, South Africa, and India.DesignData on the cost of active pharmaceutical ingredients (APIs) exported from India were extracted from an online database of customs declarations (www.infodriveindia.com). A formula was designed to use API price data to estimate a cost-based price, by adding the costs of converting API to a finished pharmaceutical product, including the cost of formulation in vials or ampoules, transportation and an average profit margin.ResultsFor injectable formulations on the WHO EML, medicines had prices above the estimated cost-based price in 77% of comparisons in England (median ratio 2.54), and 62% in South Africa (median ratio 1.48), while 85% of medicines in India had prices below estimated cost-based price (median ratio 0.30). 19% of injectable medicines in England, 9% in South Africa, and 5% in India had prices more than 10 times the estimated cost-based price. Medicines that appeared in the top 20 by ratio of lowest current price to estimated cost-based price for more than one country included numerous oncology medicines-irinotecan, leuprorelin, ifosfamide, daunorubicin, filgrastim and mesna-as well as valproic acid and ciclosporin.ConclusionsEstimating manufacturing costs can identify cases in which profit margins for medicines may be set significantly higher than average.
| S-EPMC6773329 | biostudies-literature
Project description:There is growing need to develop efficient methods for early-stage drug discovery, continuous manufacturing of drug delivery vehicles, and ultra-precise dosing of high potency drugs. Here we demonstrate the use of solvent-free organic vapor jet printing to deposit nanostructured films of small molecular pharmaceutical ingredients, including caffeine, paracetamol, ibuprofen, tamoxifen, BAY 11-7082 and fluorescein, with accuracy on the scale of micrograms per square centimeter, onto glass, Tegaderm, Listerine tabs, and stainless steel microneedles. The printed films exhibit similar crystallographic order and chemistry as the original powders; controlled, order-of-magnitude enhancements of dissolution rate are observed relative to powder-form particles. In vitro treatment of breast and ovarian cancer cell cultures in aqueous media by tamoxifen and BAY 11-7082 films shows similar behavior to drugs pre-dissolved in dimethyl sulfoxide. The demonstrated precise printing of medicines as films, without the use of solvents, can accelerate drug screening and enable continuous manufacturing, while enhancing dosage accuracy.Traditional approaches used in the pharmaceutical industry are not precise or versatile enough for customized medicine formulation and manufacture. Here the authors produce a method to form coatings, with accurate dosages, as well as a means of closely controlling dissolution kinetics.
| S-EPMC5617892 | biostudies-other
Project description:Anemia is a major source of morbidity and mortality worldwide. Here we review recent insights into how red blood cells (RBCs) are produced, the pathogenic mechanisms underlying various forms of anemia, and novel therapies derived from these findings. It is likely that these new insights, mainly arising from basic scientific studies, will contribute immensely to both the understanding of frequently debilitating forms of anemia and the ability to treat affected patients. Major worldwide diseases that are likely to benefit from new advances include the hemoglobinopathies (?-thalassemia and sickle cell disease); rare genetic disorders of RBC production; and anemias associated with chronic kidney disease, inflammation, and cancer. Promising new approaches to treatment include drugs that target recently defined pathways in RBC production, iron metabolism, and fetal globin-family gene expression, as well as gene therapies that use improved viral vectors and newly developed genome editing technologies.
| S-EPMC4452951 | biostudies-literature