Nucleic Acid-based Biomarkers Research Articles

Nucleic Acids-Based Biomarkers for Alzheimer's Disease Diagnosis and Novel Molecules to Treat the Disease.

Alzheimer's disease (AD) represents the most common form of dementia and affects million people worldwide, with a high social burden and considerable economic costs. AD diagnosis benefits from a well-established panel of laboratory tests that allow ruling-in patients, along with FDG and amyloid PET imaging tools. The main laboratory tests used to identify AD patients are Aβ40, Aβ42, the Aβ42/Aβ40 ratio, phosphorylated Tau 181 (pTau181) and total Tau (tTau). Although they are measured preferentially in the cerebrospinal fluid (CSF), some evidence about the possibility for blood-based determination to enter clinical practice is growing up. Unfortunately, CSF biomarkers for AD and, even more, the blood-based ones, present a few flaws, and twenty years of research in this field did not overcome these pitfalls. The tale even worsens when the issue of treating AD is addressed due to the lack of effective strategies despite the many decades of attempts by pharmaceutic industries and scientists. Amyloid-based drugs failed to stop the disease, and no neuroinflammation-based drugs have been demonstrated to work so far. Hence, only symptomatic therapy is available, with no disease-modifying treatment on hand. Such a desolate situation fully justifies the active search for novel biomarkers to be used as reliable tests for AD diagnosis and molecular targets for treating patients. Recently, a novel group of molecules has been identified to be used for AD diagnosis and follow-up, the nuclei acid-based biomarkers. Nucleic acid-based biomarkers are a composite group of extracellular molecules consisting of DNA and RNA alone or in combination with other molecules, including proteins. This review article reports the main findings from the studies carried out on these biomarkers during AD, and highlights their advantages and limitations.

Advanced Evanescent-Wave Optical Biosensors for the Detection of Nucleic Acids: An Analytic Perspective.

Evanescent-wave optical biosensors have become an attractive alternative for the screening of nucleic acids in the clinical context. They possess highly sensitive transducers able to perform detection of a wide range of nucleic acid-based biomarkers without the need of any label or marker. These optical biosensor platforms are very versatile, allowing the incorporation of an almost limitless range of biorecognition probes precisely and robustly adhered to the sensor surface by covalent surface chemistry approaches. In addition, their application can be further enhanced by their combination with different processes, thanks to their integration with complex and automated microfluidic systems, facilitating the development of multiplexed and user-friendly platforms. The objective of this work is to provide a comprehensive synopsis of cutting-edge analytical strategies based on these label-free optical biosensors able to deal with the drawbacks related to DNA and RNA detection, from single point mutations assays and epigenetic alterations, to bacterial infections. Several plasmonic and silicon photonic-based biosensors are described together with their most recent applications in this area. We also identify and analyse the main challenges faced when attempting to harness this technology and how several innovative approaches introduced in the last years manage those issues, including the use of new biorecognition probes, surface functionalization approaches, signal amplification and enhancement strategies, as well as, sophisticated microfluidic solutions.

Liquid biopsies for omics-based analysis in sentinel mussels.

Liquid biopsy of plasma is a simple and non-invasive technology that holds great promise in biomedical research. It is based on the analysis of nucleic acid-based biomarkers with predictive potential. In the present work, we have combined this concept with the FTA technology for sentinel mussels. We found that hemocytes collected from liquid biopsies can be readily fixed on FTA cards and used for long-term transcriptome analysis. We also showed that liquid biopsy is easily adaptable for metagenomic analysis of bacterial profiles of mussels. We finally provide evidence that liquid biopsies contained circulating cell-free DNA (ccfDNA) which can be used as an easily accessible genomic reservoir. Sampling of FTA-fixed circulating nucleic acids is stable at room temperature and does not necessitate a cold-chain protection. It showed comparable performance to frozen samples and is ideally adapted for sampling in remote areas, most notably in polar regions threatened by anthropogenic activities. From an ethical point of view, this minimally-invasive and non-lethal approach further reduces incidental mortality associated with conventional tissue sampling. This liquid biopsy-based approach should thus facilitate biobanking activities and development of omics-based biomarkers in mussels to assess the quality of aquatic ecosystems.

Biomarkers of β-Cell Stress and Death in Type 1 Diabetes.

The hallmark of type 1 diabetes (T1D) is a decline in functional β-cell mass arising as a result of autoimmunity. Immunomodulatory interventions at disease onset have resulted in partial stabilization of β-cell function, but full recovery of insulin secretion has remained elusive. Revised efforts have focused on disease prevention through interventions administered at earlier disease stages. To support this paradigm, there is a parallel effort ongoing to identify circulating biomarkers that have the potential to identify stress and death of the islet β-cells. Whereas no definitive biomarker(s) have been fully validated, several approaches hold promise that T1D can be reliably identified in the pre-symptomatic phase, such that either β-cell preservation or immunomodulatory agents might be employed in at-risk populations. This review summarizes the most promising protein- and nucleic acid-based biomarkers discovered to date and reviews the context in which they have been studied.

Nucleic acid biomarkers of β cell stress and death in type 1 diabetes

The purpose of this review is to summarize recent advances in the development of nucleic acid-based biomarkers of type 1 diabetes (T1D). Recent rodent and human studies have identified new roles for stress pathways intrinsic to the β cell during the development of T1D. As such, methods to identify an authentic nucleic acid signature of β cell stress and/or death may improve our ability to predict T1D at earlier timepoints, allowing for optimal timing of immunomodulatory interventions. To this end, both targeted and unbiased approaches have begun to identify changes in microRNA expression patterns in T1D. Moreover, a number of groups have developed distinct assays that quantitatively detect circulating unmethylated insulin DNA, which is thought to primarily emanate from dying β cells. Here we highlight unique blood and urine microRNA signatures identified in T1D cohorts, compare differences between first, second, and third-generation assays that detect circulating unmethylated insulin DNA, and review recent technological advances that have the capacity to improve T1D biomarker development.

Bionanotechnology and Nanomedicine

This special issue contains contributions from the broad interdisciplinary fields of bionanotechnology and nanomedicine. Nanotechnology has great promise in biology and medicine. This includes new approaches to fundamental studies, improved methods for detection of protein or nucleic acid-based biomarkers of disease, and new ways to administer drugs or vaccines or enhancing their effects. The tools of nanotechnology provide new insights into mechanisms of normal biological functions and diseases. Novel nanotechnology-based imaging methods reveal structural and functional information at progressively higher levels of resolution, both in vitro, in cells and in organisms. Molecular components of biological systems on their own can be often viewed as nanoscale machines with functions that have been tuned through evolution and with design principles often based on self-assembly and self-organization phenomena. These biological nanomachines can be incorporated into micro- and nanofabricated devices, a merger that yields novel structures and functionalities.

Noninvasive Prediction of Organ Graft Rejection and Outcome Using Gene Expression Patterns

Development of predictive, diagnostic, and prognostic biomarkers of allograft status and outcome is important and challenging, and may be rewarded with individualized therapy for the organ graft recipient. Herein, we summarize noninvasive messenger RNA profiling studies for ascertaining allograft status and outcome. Nucleic acid-based biomarkers of allograft status have been developed by several laboratories, but the studies have primarily been single center investigations. Ongoing multicenter trials including the Clinical Trials in Organ Transplantation (https://www.ctotstudies.org) should help further to define the clinical utility of noninvasively developed messenger RNA profiles as biomarkers of allograft status and outcome.