Search results for "non-viral"

SOLID LIPID NANOPARTICLES FOR APPLICATIONS IN GENE THERAPY: A REVIEW OF THE STATE OF THE ART

2010

Importance of the field. Gene therapy represents a new paradigm in the prevention and treatment of many inherited and acquired diseases, including genetic disorders, such as cystic fibrosis, haemophilia and many somatic diseases, such as tumours, neurodegenerative diseases and viral infections, such as AIDS. Areas covered in this review. Among a large array of non-viral transfection agents used for in-vitro applications, cationic SLNs are the topic of this review, being recently proposed as an alternative carrier for DNA delivery, due to many technological advantages such as large-scale production from substances generally recognized as safe, good storage stability and possibility of steam …

Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 i…

2012

Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T cells (Treg) o…

BIOCOMPATIBLE POLYAMINOACID-BASED POLYCATIONS AS NON-VIRAL VECTORS FOR GENE THERAPY OF CYSTIC FIBROSIS.

2009

DEVELOPMENT OF S/MAR MINICIRLES VECTOR FOR PERSISTENT EXPRESSION IN VIVO.

2009

An ideal vector for gene therapy must fulfil the following requirements: non-toxicity, mitotic stability and persistent therapeutic levels of transgene expression. Viral vectors are widely used due to their ability to sustain prolonged expression. Their potentially tumorigenic effects are a limiting factor for in vivo applications. Non-viral vectors, which can be designed to be free from viral sequences, are a promising alternative for gene transfer although they often produce transient transgene expression. This limitation of this vector type is primarily due to bacterial sequences they contain and these have proven to be toxic for the mammalian cells as they contain a high number of unmet…

Well-defined polypeptide-based systems as non-viral vectors for cytosolic delivery

2017

A convenient cytosolic drug delivery constitutes a very powerful tool for the treatment and/or prevention of several relevant human diseases. Along with recent advances in therapeutic technologies based on biomacromolecules (e.g. oligonucleotides or proteins), we also require the development of technologies which improve the transport of therapeutic molecules to the cell of choice. This has led to the emergence of a variety of promising methods over the last 20 years. Despite significant progress, these methods still suffer from several shortcomings including low/variable delivery efficiency, high cytotoxicity, and perhaps most importantly, ineffective endosomal/lysosomal escape. In this co…

Development of S/MAR plasmid vector for persistent expression and maintenance in vivo

2007

An ideal gene therapy vector should enable persistent transgene expression without limitations of safety and reproducibility. Here we report the development of a non-viral episomal plasmid DNA (pDNA) vector that appears to fulfil these criteria. This pDNA vector combines a scaffold/matrix attachment region (S/MAR) with a human liver-specific promoter (a1-antitrypsin (AAT)) in such a way that long-term expression is enabled in murine liver following hydrodynamic injection. Long-term expression is demonstrated by monitoring the longitudinal luciferase expression profile for up to 6 months by means of in situ bioluminescent imaging. We conclude that the combination of a mammalian, tissue-speci…

Multicompartmental Lipopolyplex as Vehicle for Antigens and Genes Delivery in Vaccine Formulations

2021

Vector design and its characterization is an area of great interest in current vaccine research. In this article, we have formulated and characterized a multicompartmental lipopolyplex, which associates multiple liposomes and polyplexes in the same complex. These particles allow the simultaneous delivery of lipid or water-soluble antigens associated with genes to the same cell, in much higher amounts than conventional lipopolyplexes. The vector characterization and optimization were carried out using liposomes with entrapped carboxyfluorescein and adapted electrophoretic assays. Two types of lipopolyplexes (containing hydrophilic or lipophilic antigens) were employed to evaluate their inter…

Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

2020

[EN] Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large on…

Development of S/MAR minicircles for enhanced and persistent transgene expression in the mouse liver.

2010

We have previously described the development of a scaffold/matrix attachment region (S/MAR) episomal vector system for in vivo application and demonstrated its utility to sustain transgene expression in the mouse liver for at least 6 months following a single administration. Subsequently, we observed that transgene expression is sustained for the lifetime of the animal. The level of expression, however, does drop appreciably over time. We hypothesised that by eliminating the bacterial components in our vectors, we could improve their performance since bacterial sequences have been shown to be responsible for the immunotoxicity of the vector and the silencing of its expression when applied i…

Desarrollo de competencias profesionales en biomedicina utilizando el aprendizaje basado en proyectos

2019

[EN] Professional competences in the field of experimental sciences are acquired through the practice of professional practice. In the university environment, the knowledge, skills and abilities in the different undergraduate subjects are taught in a parceled manner. Our 45 students biotechnology studies in Catholic University of Valencia, during the internship repeat protolocos and follow a recipe to perform an experiment that exemplifies the fundamental contents of the subject being taught. The aboradaje of this work is based on project-based learning. The student has to elaborate a biotechnological project from beginning to end. The project is based on the construction of a non-viral vec…