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Biomedicine & Pharmacotherapy =... Dec 2020Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a...
Aptamers are single-stranded nucleic acid sequences that can bind to target molecules with high selectivity and affinity. Most aptamers are screened in vitro by a combinatorial biology technique called systematic evolution of ligands by exponential enrichment (SELEX). Since aptamers were discovered in the 1990s, they have attracted considerable attention and have been widely used in many fields owing to their unique advantages. In this review, we present an overview of the advancements made in aptamers used for biosensors and targeted therapy. For the former, we will discuss multiple aptamer-based biosensors with different principles detected by various signaling methods. For the latter, we will focus on aptamer-based targeted therapy using aptamers as both biotechnological tools for targeted drug delivery and as targeted therapeutic agents. Finally, challenges and new perspectives associated with these two regions were further discussed. We hope that this review will help researchers interested in aptamer-related biosensing and targeted therapy research.
Topics: Animals; Antineoplastic Agents; Aptamers, Nucleotide; Biomarkers, Tumor; Biosensing Techniques; Drug Carriers; Drug Delivery Systems; Gene Transfer Techniques; Humans; Nanoparticles; Neoplasms; Predictive Value of Tests; RNA, Small Interfering; RNAi Therapeutics; SELEX Aptamer Technique
PubMed: 33096353
DOI: 10.1016/j.biopha.2020.110902 -
Gene Therapy Sep 2022Spinal muscular atrophy (SMA) is a severe childhood neuromuscular disease for which two genetic therapies, Nusinersen (Spinraza, an antisense oligonucleotide), and... (Meta-Analysis)
Meta-Analysis
Spinal muscular atrophy (SMA) is a severe childhood neuromuscular disease for which two genetic therapies, Nusinersen (Spinraza, an antisense oligonucleotide), and AVXS-101 (Zolgensma, an adeno-associated viral vector of serotype 9 AAV9), have recently been approved. We investigated the pre-clinical development of SMA genetic therapies in rodent models and whether this can predict clinical efficacy. We have performed a systematic review of relevant publications and extracted median survival and details of experimental design. A random effects meta-analysis was used to estimate and compare efficacy. We stratified by experimental design (type of genetic therapy, mouse model, route and time of administration) and sought any evidence of publication bias. 51 publications were identified containing 155 individual comparisons, comprising 2573 animals in total. Genetic therapies prolonged survival in SMA mouse models by 3.23-fold (95% CI 2.75-3.79) compared to controls. Study design characteristics accounted for significant heterogeneity between studies and greatly affected observed median survival ratios. Some evidence of publication bias was found. These data are consistent with the extended average lifespan of Spinraza- and Zolgensma-treated children in the clinic. Together, these results support that SMA has been particularly amenable to genetic therapy approaches and highlight SMA as a trailblazer for therapeutic development.
Topics: Animals; Disease Models, Animal; Genetic Therapy; Mice; Muscular Atrophy, Spinal; Oligonucleotides, Antisense; Rodentia; Treatment Outcome
PubMed: 34611322
DOI: 10.1038/s41434-021-00292-4 -
Langmuir : the ACS Journal of Surfaces... Jun 2015Biosensors are ideally portable, low-cost tools for the rapid detection of pathogens, proteins, and other analytes. The global biosensor market is currently worth over... (Review)
Review
Biosensors are ideally portable, low-cost tools for the rapid detection of pathogens, proteins, and other analytes. The global biosensor market is currently worth over 10 billion dollars annually and is a burgeoning field of interdisciplinary research that is hailed as a potential revolution in consumer, healthcare, and industrial testing. A key barrier to the widespread adoption of biosensors, however, is their cost. Although many systems have been validated in the laboratory setting and biosensors for a range of analytes are proven at the concept level, many have yet to make a strong commercial case for their acceptance. Though it is true with the development of cheaper electrodes, circuits, and components that there is a downward pressure on costs, there is also an emerging trend toward the development of multianalyte biosensors that is pushing in the other direction. One way to reduce the cost that is suitable for certain systems is to enable their reuse, thus reducing the cost per test. Regenerating biosensors is a technique that can often be used in conjunction with existing systems in order to reduce costs and accelerate the commercialization process. This article discusses the merits and drawbacks of regeneration schemes that have been proven in various biosensor systems and indicates parameters for successful regeneration based on a systematic review of the literature. It also outlines some of the difficulties encountered when considering the role of regeneration at the point of use. A brief meta-analysis has been included in this review to develop a working definition for biosensor regeneration, and using this analysis only ∼60% of the reported studies analyzed were deemed a success. This highlights the variation within the field and the need to normalize regeneration as a standard process across the field by establishing a consensus term.
Topics: Antibodies; Aptamers, Nucleotide; Biosensing Techniques; Cost-Benefit Analysis; Detergents; Electrochemical Techniques; Electrodes; Equipment Reuse; Glycine; Hydrogen-Ion Concentration; Sound; Thermodynamics
PubMed: 25402969
DOI: 10.1021/la503533g -
Cellular Physiology and Biochemistry :... 2015Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIMS
Aberrant microRNA expression has the potential to be used for early diagnosis of gastric cancer or to predict survival and treatment response. This study performed a systematic review and meta-analysis of altered miRNAs in gastric cancer in order to assess the use of miRNAs as novel biomarkers for early detection and prognosis prediction of gastric cancer.
METHODS
We retrieved published articles from the PubMed online database and obtained different sets of data on miRNAs expression profiling in gastric cancer and highlighted the most frequently dysregulated miRNAs in gastric cancer. We then extracted studies that used quantitative RT-PCR and then pooled them together by using meta-disc software (version 1.4).
RESULTS
We found that there were 47 aberrantly expressed miRNAs in gastric cancer (29 up-regulated and 18 down-regulated) that were most frequently reported in the literature. In publications that provided information on specific miRNA expression vs. diagnostic value, the pooled data showed good sensitivity and specificity as well as high levels of overall accuracy. However, specimen types could be a factor that introduces substantial heterogeneity. Published studies also showed association of altered miRNA expression with clinicopathological data from gastric cancer patients.
CONCLUSION
Thus, various miRNAs are differentially expressed in gastric cancer and some of them could be further evaluated as biomarkers for early diagnosis of gastric cancer and prediction of prognosis or treatment response.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Oligonucleotide Array Sequence Analysis; Prognosis; Stomach Neoplasms
PubMed: 25633747
DOI: 10.1159/000369750 -
Journal of Assisted Reproduction and... Jul 2016The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a... (Review)
Review
PURPOSE
The purpose of the review was to define the various diagnostic platforms currently available to perform preimplantation genetic testing for aneuploidy and describe in a clear and balanced manner the various strengths and weaknesses of these technologies.
METHODS
A systematic literature review was conducted. We used the terms "preimplantation genetic testing," "preimplantation genetic diagnosis," "preimplantation genetic screening," "preimplantation genetic diagnosis for aneuploidy," "PGD," "PGS," and "PGD-A" to search through PubMed, ScienceDirect, and Google Scholar from the year 2000 to April 2016. Bibliographies of articles were also searched for relevant studies. When possible, larger randomized controlled trials were used. However, for some emerging data, only data from meeting abstracts were available.
RESULTS
PGS is emerging as one of the most valuable tools to enhance pregnancy success with assisted reproductive technologies. While all of the current diagnostic platforms currently available have various advantages and disadvantages, some platforms, such as next-generation sequencing (NGS), are capable of evaluating far more data points than has been previously possible. The emerging complexity of different technologies, especially with the utilization of more sophisticated tools such as NGS, requires an understanding by clinicians in order to request the best test for their patients..
CONCLUSION
Ultimately, the choice of which diagnostic platform is utilized should be individualized to the needs of both the clinic and the patient. Such a decision must incorporate the risk tolerance of both the patient and provider, fiscal considerations, and other factors such as the ability to counsel patients on their testing results and how these may or may not impact clinical outcomes.
Topics: Aneuploidy; Blastocyst; Female; Fertilization in Vitro; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Pregnancy; Preimplantation Diagnosis; Real-Time Polymerase Chain Reaction
PubMed: 27299602
DOI: 10.1007/s10815-016-0740-2 -
Critical Reviews in Analytical Chemistry 2022Diabetes mellitus is known as an epidemic problem of public health in worldwide. According to the reports of International Diabetes Federation, the global number of... (Review)
Review
Diabetes mellitus is known as an epidemic problem of public health in worldwide. According to the reports of International Diabetes Federation, the global number of diabetic adults has been growing annually. Unfortunately, millions of diabetes cases may remain undiagnosed every year. Unfortunately, the glucose level of blood can be fluctuated by lifestyle. So, development of reliable, simple and fast response diagnostic methods is urgently required. Aptamer-based sensors have been recently developed as a sensitive and fast method for the diagnosis and detection of diabetes. We systematically checked the scientific literature including studies related to aptasensors as a diagnostic tool for diabetes. Many electronic databases such as Google Scholar, Scopus, PubMed and Science Direct were searched up to 2020. The present study obviously demonstrates important and unavoidable role of aptasensors as a potential technique for the diagnosis of diabetes. Different aptasenosrs such as optical, mass-related, microfluidic, and electrochemical aptasenors were successfully designed for diagnosis of diabetic biomarkers in desired range which is necessary for diagnosis or pre-diagnosis of diabetes. Although the introduced aptasensors were interestingly useful for detection of biomarkers in biological samples, but some defects may limit the incorporation of aptasensors, especially optical, mass-related, and microfluidic types, and lateral flow strips with point-of-care test (POCT) method which is necessary for self-controlling the diabetes. The results obviously demonstrate that electrochemical aptasensors, specially label-free types, due to the unbelievable sensitivity and easy to fabrication can be a promising methods for designing the POCT chips to diagnosis the diabetic biomarkers.
Topics: Humans; Aptamers, Nucleotide; Biomarkers; Biosensing Techniques; Diabetes Mellitus; Electrochemical Techniques
PubMed: 34254847
DOI: 10.1080/10408347.2021.1919986 -
Muscle & Nerve Mar 2022Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized... (Review)
Review
Duchenne muscular dystrophy (DMD) is associated with progressive muscle weakness, loss of ambulation (LOA), and early mortality. In this review we have synthesized published data on the clinical course of DMD by genotype. Using a systematic search implemented in Medline and Embase, 53 articles were identified that describe the clinical course of DMD, with pathogenic variants categorizable by exon skip or stop-codon readthrough amenability and outcomes presented by age. Outcomes described included those related to ambulatory, cardiac, pulmonary, or cognitive function. Estimates of the mean (95% confidence interval) age at LOA ranged from 9.1 (8.7-9.6) years among 90 patients amenable to skipping exon 53 to 11.5 (9.5-13.5) years among three patients amenable to skipping exon 8. Although function worsened with age, the impact of genotype was less clear for other outcomes (eg, forced vital capacity and left ventricular ejection fraction). Understanding the distribution of pathogenic variants is important for studies in DMD, as this research suggests major differences in the natural history of disease. In addition, specific details of the use of key medications, including corticosteroids, antisense oligonucleotides, and cardiac medications, should be reported.
Topics: Child; Dystrophin; Genotype; Humans; Muscular Dystrophy, Duchenne; Stroke Volume; Ventricular Function, Left
PubMed: 34878187
DOI: 10.1002/mus.27463 -
Cancers Jan 2021Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of... (Review)
Review
Transforming growth factor β (TGFβ) is a pleiotropic cytokine that participates in a wide range of biological functions. The alterations in the expression levels of this factor, or the deregulation of its signaling cascade, can lead to different pathologies, including cancer. A great variety of therapeutic strategies targeting TGFβ, or the members included in its signaling pathway, are currently being researched in cancer treatment. However, the dual role of TGFβ, as a tumor suppressor or a tumor-promoter, together with its crosstalk with other signaling pathways, has hampered the development of safe and effective treatments aimed at halting the cancer progression. This systematic literature review aims to provide insight into the different approaches available to regulate TGFβ and/or the molecules involved in its synthesis, activation, or signaling, as a cancer treatment. The therapeutic strategies most commonly investigated include antisense oligonucleotides, which prevent TGFβ synthesis, to molecules that block the interaction between TGFβ and its signaling receptors, together with inhibitors of the TGFβ signaling cascade-effectors. The effectiveness and possible complications of the different potential therapies available are also discussed.
PubMed: 33498521
DOI: 10.3390/cancers13030379 -
American Journal of Medical Genetics.... Sep 2016Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about... (Meta-Analysis)
Meta-Analysis Review
Over the last decade, several advances in ultrasound techniques, increasing availability of whole genome microarray testing, and overall expansion of our knowledge about the human genome have drastically enhanced our ability to detect chromosomal abnormalities prenatally. Despite that, genotype-phenotype correlation is difficult to establish for many chromosomal aberrations, particularly for those that are rare, as it requires thorough analysis of a significant number of cases. This in turn increases the burden of the obstetric provider to appropriately counsel a patient regarding prognosis and pregnancy options in these complicated situations. Our experience in prenatal diagnosis and management of a fetus with multiple anomalies and partial trisomy for the 14q11-q24.2 prompted a comprehensive analysis of the relevant literature. Although complete non-mosaic trisomy 14 is associated with first trimester miscarriages, partial trisomy 14q is a rare condition with undefined genotype-phenotype correlation, preventing accurate prenatal counseling, and informed decision making. We performed a systematic literature review, that aimed to summarize prenatal and postnatal findings of individual case reports on 51 patients with partial trisomy 14q in order to elucidate genotype-phenotype correlation, and to supply healthcare professionals with recommendation on essential fetal and parental testing for accurate diagnosis, pregnancy outcomes, and proper family counseling. Comparison of the clinical findings among the patients with partial 14q trisomy suggest that the resulting phenotype is likely to be influenced by the extent of the 14q trisomy segment, associated chromosomal imbalances, parental origin of the rearrangement, and dosage of the genes within the imprinted 14q32 cluster. © 2016 Wiley Periodicals, Inc.
Topics: Chromosomes, Human, Pair 14; Comparative Genomic Hybridization; Disease Management; Female; Genetic Association Studies; Genetic Counseling; Genetic Testing; Humans; In Situ Hybridization, Fluorescence; Oligonucleotide Array Sequence Analysis; Polymorphism, Single Nucleotide; Pregnancy; Pregnancy Outcome; Trisomy; Ultrasonography, Prenatal
PubMed: 27286879
DOI: 10.1002/ajmg.a.37793 -
Yonsei Medical Journal Mar 2018Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Molecular testing in non-small cell lung cancer (NSCLC) aids in identifying oncogenic alterations. The aim of this study was to compare the rates of detection of oncogenic alterations and responsiveness to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) according to EGFR mutation status as determined by peptide nucleic acid (PNA) clamping or direct sequencing (DS).
MATERIALS AND METHODS
We performed a systematic literature search using MEDLINE, EMBASE, and the Cochrane Central Register. Data from included studies were pooled to yield summary sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and receiver operating characteristic curves. A meta-regression analysis was conducted to identify potential sources of heterogeneity between selected studies.
RESULTS
We identified 10 studies comprising 924 patients. Oncogenic alterations were detected in 340 of 924 cases (36.8%) with PNA clamping and in 250 of 924 (27.1%) with DS. The pooled sensitivities of PNA clamping and DS were 0.93 [95% confidence interval (CI): 0.90-0.95] and 0.69 (95% CI: 0.64-0.73), respectively. According to meta-regression analysis, none of the covariates were found to be significant sources of heterogeneity. With respect to treatment responses to EGFR-TKIs, there was no significant difference therein between EGFR mutations detected by PNA clamping and DS (53.4% vs. 50.8%; risk ratio, 0.99; 95% CI 0.83-1.19; p=0.874).
CONCLUSION
We demonstrated that PNA clamping has a higher sensitivity than DS for detecting oncogenic alterations in NSCLC. Our findings suggest that PNA clamping is a more useful method for clinical practice.
Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Constriction; ErbB Receptors; Humans; Lung Neoplasms; Molecular Diagnostic Techniques; Mutation; Peptide Nucleic Acids; Protein Kinase Inhibitors; Receptor Protein-Tyrosine Kinases; Sensitivity and Specificity; Sequence Analysis; Sequence Analysis, DNA; Translocation, Genetic
PubMed: 29436188
DOI: 10.3349/ymj.2018.59.2.211