Lentivirus-derived vectors are among the most promising viral vectors for gene therapy currently available, but their use in clinical practice is limited by the associated risk of insertional mutagenesis. We have overcome this problem by developing a nonintegrative lentiviral vector derived from HIV type 1 with a class 1 integrase (IN) mutation (replacement of the 262RRK motif by AAH). We gener...

Retrovirus vectors [direct orientation (DO) vectors] that permit the simultaneous expression of an inserted protein-coding sequence and a dominant-acting selectable marker have been constructed. In these vectors, an internal simian virus 40 or human metallothionein promoter sequence serves to drive the expression of the bacterial neomycin phosphotransferase or guanine-xanthine phosphoribosyltra...

The novel viral vectors PVX-CP AltMV and PVXdt-CP AltMV are superexpressors of the capsid protein (CP). These viral vectors were constructed on the basis of the potato virus X (PVX) genome andAlternantheramosaic virus (AltMV) CP gene. The expression, based on the hybrid viral vectors, is genetically safe, since the systemic transport and formation of infective viral particles are blocked. CP Al...

DNA viruses are often used as vectors for foreign gene expression, but large DNA region from cloned or authentic viral genomes must usually be handled to generate viral vectors. Here, we present a unique system for generating adenoviral vectors by directly substituting a gene of interest in a small transfected plasmid with a replaced gene in a replicating viral genome in Cre-expressing 293 cell...

there is increasing trend in using recombinant stem cells as novel therapeutic candidates in different diseases. these studies encompass different applications from targeted homing of mesenchymal stromal (stem) cells (msc), to arming them with different cytokines. resistance to transfection or transduction methods had urged researchers to look for better gene delivery alternates and optimizing ...

With an increased prevalence and understanding of central nervous system (CNS) injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver...

Gene-directed tissue repair offers the clinician, human or veterinary, the chance to enhance cartilage regeneration and repair at a molecular level. Non-viral plasmid vectors have key biosafety advantages over viral vector systems for regenerative therapies due to their episomal integration however, conventional non-viral vectors can suffer from low transfection efficiency. Our objective was to...

Norwalk virus and human papilloma virus, two viruses that infect humans at mucosal surfaces, have been found capable of rapidly penetrating human mucus secretions. Viral vectors for gene therapy of Cystic Fibrosis (CF) must similarly penetrate purulent lung airway mucus (sputum) to deliver DNA to airway epithelial cells. However, surprisingly little is known about the rates at which gene delive...

The host immune responses, including T lymphocytes mediated immune response and humoral immune responses are the important parts of the challenges in gene therapy. There are some potential immunostimulants in gene delivery systems, such as viral and non-viral vectors. Viral gene products, transgene products, viral proteins derived from viral particles required by dead-end infection, and CpG DNA...

Duchenne Muscular Dystrophy (DMD) is an inherited muscle disease that is characterized by a lack of dystrophin expression in the membrane cytoskeleton of muscle fibers. This lack of dystrophin is responsible for muscle fiber necrosis which leads to the muscle atrophy and progressive muscle weakness, characteristic of the DMD pathology. Myoblast transplantation and gene therapy based on viral ve...