Los aptámeros como novedosa herramienta diagnóstica y terapéutica y su potencial uso en parasitología / Aptamers as a novel diagnostic and therapeutic tool and their potential use in parasitology

Los aptámeros son secuencias de ADN o ARN de cadena sencilla que adoptan la forma de estructuras tridimensionales únicas, lo cual les permite reconocer un blanco específico con gran afinidad. Sus usos potenciales abarcan, entre otros, el diagnóstico de enfermedades, el desarrollo de nuevos agentes terapéuticos, la detección de riesgos alimentarios, la producción de biosensores, la detección de toxinas, el transporte de fármacos en el organismo y la señalización de nanopartículas. El pegaptanib es el único aptámero aprobado para uso comercial por la Food and Drug Administration (FDA). Otros aptámeros para el tratamiento de enfermedades están en la fase clínica de desarrollo. En parasitología, se destacan los estudios que se vienen realizando en Leishmania spp., con la obtención de aptámeros que reconocen la proteína de unión a poliA (LiPABP) y que pueden tener potencial utilidad en la investigación, el diagnóstico y el tratamiento de la leishmaniasis. En cuanto a la malaria, se han obtenido aptámeros que permiten identificar eritrocitos infectados e inhiben la formación de rosetas, y otros que prometen ser alternativas para el diagnóstico al detectar de forma específica la proteína lactato deshidrogenasa (PfLDH). Para Cryptosporidium parvuum se han seleccionado aptámeros que detectan ooquistes a partir de alimentos o aguas contaminadas. Para Entamoeba histolytica se han aislado dos aptámeros llamados C4 y C5, que inhiben la proliferación in vitro de los trofozoítos y tienen potencial terapéutico. Los aptámeros contra Trypanosoma cruzi inhiben la invasión de células LLC-MK2 (de riñón de mono) en un 50 a 70 % y aquellos contra T. brucei transportan moléculas tóxicas al lisosoma parasitario como una novedosa estrategia terapéutica. Los datos recopilados en esta revisión destacan los aptámeros como una alternativa para la investigación, el diagnóstico y el tratamiento contra parásitos de interés nacional.

Aptamers are single-stranded DNA or RNA sequences that adopt unique three-dimensional structures that allow them to recognize a specific target with high affinity. They can potentially be used for the diagnosis of diseases, as new therapeutic agents, for the detection of food risks, as biosensors, for the detection of toxins, and as drug carriers and nanoparticle markers, among other applications. To date, an aptamer called pegaptanib is the only aptamer approved by the Food and Drug Administration (FDA) for commercial use. Other aptamers are in different clinical stages of development for the treatment of different diseases. In parasitology, investigations carried out with parasites such as Leishmania spp. allowed the acquisition of aptamers that recognize the polyA-binding protein LiPABP and may have potential applications in research and diagnosis and even as therapeutic agents. Regarding malaria, aptamers have been obtained that allow the identification of infected erythrocytes or inhibit the formation of rosettes, along with those that provide promising alternatives for diagnosis by specifically detecting the protein lactate dehydrogenase (PfLDH). In Cryptosporidium parvum allow the detection of oocysts in contaminated food or water. In Entamoeba histolytica, two aptamers called C4 and C5, which inhibit the proliferation of trophozoites in vitro and have potential use as therapeutic agents, have been isolated. Aptamers obtained against Trypanosoma cruzi inhibit the invasion of LLC-MK2 (from monkey kidney) cells by 50-70%, and in T. brucei, aptamers with the potential to transport toxic molecules to the parasitic lysosome were identified as a novel therapeutic strategy. The data collected in this review highlight aptamers as a novel alternative in the research, diagnosis, and treatment of parasites of national interest.

Nucleic acid aptamer and its research progress in glioma / 国际肿瘤学杂志

Nucleic acid aptamer is an oligonucleotide generated by the systematic evolution of ligands by exponential enrichment (SELEX)process from oligonucleotide library.Nucleic acid aptamer can bind to various targets with high specificity and can recognize or inhibit the biological activity of targeting molecular. Glioma-specific aptamers are developed by either targeting the glioma cells or known biomarkers,which can be coupled with nanoparticles,drugs or molecular probes,and can be applied in the imaging,targeted therapy and drug delivery of glioma.

Review of Studies on the Chinese Medicine combined with Nucleoside (acid) Drugs for Chronic Hepatitis B / 国际中医中药杂志

Recent studies showed that Chinese medicine combined with nucleoside (acid) treatments could benefit chronic hepatitis B (CHB). Many patients have gained the benefits from these treatments. This paper summarized the recent studies of Chinese medicine combined with nucleoside (acid) drugs for chronic hepatitis B, and discussed the status of the researches, in order to explore an integrated treatment for chronic hepatitis B.

Aptamer and its therapeutic applications for age-related macular degeneration / 中华眼底病杂志

Vascular endothelial growth factor (VEGF),platelet derived growth factor (PDGF) and complements play key roles in the pathogenesis of age-related macular degeneration (AMD).Pegaptanib,the first therapeutic aptamer against VEGF165,has been approved by the Food and Drug Administration (FDA) of US for the treatment of exudative AMD.Another two aptamers El0030 and ARC1905,each target PDGF-B and complement C5 respectively,are undergoing clinical trials.Recent trends to treat AMD are combined therapies targeting multiple key molecules in the pathogenesis of AMD;aptamers against multiple targets may become the preferred drug for AMD.

Nucleic acid aptamer for caner therapeutics and diagnostics / 国际肿瘤学杂志

Nucleic acid aptamer is the systematic evolution of ligands by exponential enrichment syn-thesized in vitro screening technology resulting single-stranded oligonucleotides (DNA or RNA),by folding into unique spatial structure specific recognition binding target molecules.Aptamers function is similar to the anti-bodies but more specifically,as novel molecular probes for the field of cancer therapeutics and diagnostics.

Aptamers as molecular probes in tumor molecular imaging / 国际肿瘤学杂志

The ideal molecular imaging probe should have characteristics of specificity,sensitivity and safety.Aptamers are sing-strand DNA or RNA oligonucleotides which can bind their targets with high specificity and high affinity.Aptamers are new types of molecular imaging probe because they have many advantages,such as their large sum of possible targets,small molecule weights,easily production and modification,low immuno-genicity,high tissue penetration and so on.Now more and more aptamers research on tumor molecular imaging provides a new technology and tool for tumor diagnosis and therapy.

Study on the in vitro targeting and imaging performance of aptamer modified targeted ultrasound/photoacoustic dual-modality contrast agent / 中华超声影像学杂志

Objective To study the targeting ability of aptamer-modified PLGA nanoparticle encapsulated with gold nanorod and liquid perflurocarbon,and observe its mediated ultrasound/photoacoustic dual-modality imaging in vitro.Methods PLGA nanoparticle was prepared using double emulsion technique.Aptamer-modified PLGA nanoparticle was obtained by connecting,then PLGA nanoparticle was conjugated with MUC1 aptamer carbodiimide technique aimed to obtain aptamer-modified PLGA nanoparticle.Targeting ability of aptamer-modified PLGA nanoparticle to MCF-7 tumor cells in vitro was tested by fluorescence microscope.Besides,there were three control groups including PLGA nanoparticle group,aptamer group and HELA cell group.A commercial photoacoustic instrument was used to detect ultrasound/photoacoustic signal.Results A significant number of aptamer-modified PLGA nanoparticles gathered around the MCF-7 cells,however,the specific binding can not be observed in control groups.Both ultrasound and photoacoustic signal intensity of the aptamer-modified PLGA nanoparticles increased significantly when excited with laser.Conclusions The aptamer-modified PLGA nanoparticle was successfully prepared,and had superior targeting ability to MCF-7 cells,Morever,ultrasound/photoacoustic signal emitted the by nanoparticle increased significantly.These properties make the targeted nanoparticle a great potential to become a distinguished uhrasound/photoacoustic dual modality contrast agent,which lays good foundation for further targeted imaging application in vivo.

Cotinine-conjugated aptamer/anti-cotinine antibody complexes as a novel affinity unit for use in biological assays

Aptamers are synthetic, relatively short (e.g., 20-80 bases) RNA or ssDNA oligonucleotides that can bind targets with high affinity and specificity, similar to antibodies, because they can fold into unique, three-dimensional shapes. For use in various assays and experiments, aptamers have been conjugated with biotin or digoxigenin to form complexes with avidin or anti-digoxigenin antibodies, respectively. In this study, we developed a method to label the 5' ends of aptamers with cotinine, which allows formation of a stable complex with anti-cotinine antibodies for the purpose of providing another affinity unit for the application in biological assays using aptamers. To demonstrate the functionality of this affinity unit in biological assays, we utilized two well-known aptamers: AS1411, which binds nucleolin, and pegaptanib, which binds vascular endothelial growth factor. Cotinine-conjugated AS1411/anti-cotinine antibody complexes were successfully applied to immunoblot, immunoprecipitation, and flow cytometric analyses, and cotinine-conjugated pegaptanib/anti-cotinine antibody complexes were used successfully in enzyme immunoassays. Our results show that cotinine-conjugated aptamer/anti-cotinine antibody complexes are an effective alternative and complementary technique for aptamer use in multiple assays and experiments.

Application of aptamers in the study of autoimmune diseases / 中华检验医学杂志

Aptamers are oligonucleotides or peptides those are able to bind tightly,by their specific three-dimensional shapes,to a variety of targets.Because of numerous merits ( high affinity,high specificity,small size,little immunogenicity,stable structures,and ease of synthesis),aptamers represent a valid alternative to antibodies and become a valuable research tool and show great application to fundamental research,drug selection and clinical diagnosis and therapy.The review describe the applications and the possible applications of aptamers in the diagnosis,treatment and pathogenesis of autoimmune diseases.