Vectores lipidicos. Nuevas estrategias aplicadas a la terapia génica / Lipid vectors. New strategies for gene therapy

A diferencia del resto de las moléculas biológicas, los fosfolípidos son capaces de autoensamblarse espontáneamente. Con ellos es relativamente simples generar estructuras selladas extremadamente estables, de tamaño, forma y empaquetamiento controlables, llamadas liposomas. En este artículo revisaremos el uso de liposomas para generar vectores que mejoren los procesos de transfección en células eucarioticas, tanto in vivo como in vitro. Empleando vectores lipídicos, es potencialmente posible enviar selectivamente un segmento de AND a cualquier sitio del cuerpo, forzarlo a ingresar al interior celular y aun controlar el destino intracelular de la carga transportada. La clave del éxito de la transfección por medio de vectores lipídicos radica en que protegen mecánicamente al AND de la degradación plasmática, ofreciendo a la vez la oportunidad de controlar su biodistribuición, independientemente del tamaño del segmento de AND que se quiera expresar. Asimismo, son no carcinogénicos y pobremente inmunogénicos. Los avances en la química de sintésis de lípidos permitirán construir vectores cada vez más eficientes, que capitan con los altos niveles de transfección de los vectores virales, sumado a las ventajas de extrema versatilidad, facilidad de preparación y bioseguridad propias de la moléculas autoensamblables.

La medicina molecular: ¿es una utopía pensar en su aplicación clínica? / The molecular medicine: is it an utopia to think in it clinical application?

In order to know better the diagnostics and the physiopathology of molecular, it's necessary to incorporate molecular biology techniques to an important group of illnesses, some of them are infectious pathologies and genetic illnesses. The knowledge of human metabolic ways or the specific enzymes that can be of molecular basis of the several man pathologies, is the molecular medicine. Actually, at least exist three lines that use the molecular biology in order to understand medical problems. These main lines are: 1. hereditary illnesses, II. viral and bacteriology diagnoses, and III. identification and the studies of paternity

Time-resolved emission spectroscopy as a tool to follow nucleic acid-protein interaction.

Fluorescence spectroscopy is undoubtedly a useful tool to study the structural and functional aspects of nucleic acids-protein interactions as well as the catalytic functions of particular residues of multi-subunit enzyme complexes. The dynamic interaction of nucleic acids and proteins occurring at nanosecond time scale can now be monitored by making life-time measurements or by time-resolved emission spectroscopy. These measurements are made by exploiting the intrinsic fluorescent residues in proteins i.e. W or by the use of extrinsic fluorophores which are tagged on to particular residues and that are sensitive to the microenvironment changes. In this study we describe the use of time resolved emission spectroscopy to (a) analyse the transient binding between sigma 70 and DNA by monitoring the quenching of W residues and (b) monitor the various states which nucleosomes of active, inducible or inactive chromatin may adopt in vivo.

Interaction of some fluorinated nucleic acid components with praseodymium: an absorption spectral approach.

Absorption difference and comparative absorption spectrophotometric studies on praseodymium(III) and fluorouracil, fluorocytosine, fluoroadenine, fluorothymine, fluorouridine, fluorocytidine, fluoroadenosine and fluorothymidine systems at pH approximately 5.5 and in different stoichiometries in 80% DMF medium have been carried out. Magnitudes of spectral parameters, viz. Coulombic (Fk), spin-orbit (zeta 4f), nephelauxetic (beta), bonding (b), intensity (T lambda Judd-Ofelt), and oscillator strength (P) and their variation have provided information on the binding mode of these biomolecules in terms of outer and inner sphere complexation, degree of covalency and extent of 4f orbital involvement. Preliminary ultrasonic studies have indicated that these biomolecules behave as structure breakers, hence weak ligands in aqueous medium, while strengthening water structure in semi-nonaqueous medium. The analysis of the isolated solid complexes has suggested octa- and nona-coordination for praseodymium(III) in fluorinated nucleic bases and fluorinated nucleoside complexes.

Mode of action of intercalators: a theoretical study.

Mode of action of some intercalators has been theoretically investigated on the basis of quantum mechanical perturbation method. Energies of H-bond interaction between drug chromophore and base pairs have been calculated in all possible orientations. The stacking energy has also been calculated with the base pairs. The effect of these interactions on specific recognition has also been discussed. On the basis of these studies, a model for the interaction of these drugs has been proposed. This explains the relative activities of acridine intercalators and satisfies the experimental observations.