Plank C.,TU Munich |
Eglin D.,AO Research Institute Davos |
Fahy N.,National University of Ireland |
Sapet C.,OZ Biosciences |
And 6 more authors.
European Journal of Nanomedicine | Year: 2012
The GAMBA Consortium is developing a novel gene-activated matrix platform for bone and cartilage repair with a focus on osteoarthritis-related tissue damage. The scientific and technological objectives of this project are complemented with an innovative program of public outreach, actively linking patients and society to the evolvement of this project. The GAMBA platform will implement a concept of spatiotemporal control of regenerative bioactivity on command and demand. A gene activated matrix is a biomaterial with embedded gene vectors that will genetically modify cells embedded in or colonising the matrix. The platform comprises modules that self-adapt to the biological environment and that can be independently addressed with endogenous biological and exogenous physical or pharmacological stimuli, resulting in a temporally and spatially coordinated growth factor gene expression pattern. This reproduces, within the matrix, key elements of natural tissue formation. The modules are a biomimetic hyaluronan gel, a ceramic matrix, growth factor-encoding gene vector nanoparticles, magnetic nanoparticles and mesenchymal stem cells. Anatomical adaptivity is achieved with engineered thermal properties of the polymer matrix, which embeds other modules, selected according to functional requirements. Mechanical support is provided by Micro Macroporous Biphasic Calcium Phosphate (MBCP ™ ), a resorbable material approved for clinical use. Spatiotemporal control of bioactivity and responsiveness to physiological conditions is represented, firstly, in the spatial distribution and release profiles of gene vectors within the composite matrix and, secondly, by letting local and external biological or physical stimuli activate the promoters driving the expression of vector-encoded growth factor transgenes. This concept is implemented by a multidisciplinary team from leading European institutions. Here, we report on the concepts, objectives and some preliminary results of the GAMBA project which is funded in 7th Framework Programme of the European Union THEME [NMP-2009-2.3-1], Biomimetic gels and polymers for tissue repair. © 2012 by Walter de Gruyter • Berlin • Boston.
Orlando C.,Institute for Experimental Treatment of Cystic Fibrosis |
Orlando C.,University of Zurich |
Castellani S.,University of Foggia |
Mykhaylyk O.,TU Munich |
And 6 more authors.
Journal of Gene Medicine | Year: 2010
Background: Lentiviral (LV) vectors are able to only slowly and inefficiently transduce nondividing cells such as those of the airway epithelium. To address this issue, we have exploited the magnetofection technique in in vitro models of airway epithelium. Methods: Magnetofectins were formed by noncovalent interaction between LV particles and polycation-coated iron oxide nanoparticles. Efficiency of LV-mediated transduction (as evaluated through green fluorescent protein (GFP) expression by cytofluorimetric analysis) was measured in bronchial epithelial cells in the presence or absence of a magnetic field. Cytotoxicity was evaluated by lactate dehydrogenase (LDH) release; cell monolayer integrity by measurement of transepithelial resistance (TER) and evaluation of correct zonula occludens-1 (ZO-1) localization at tight junctions (TJs) by immunofluorescence and confocal microscopy. Results: In nonpolarized cells, magnetofectins enhanced LV-mediated transduction at multiplicity of infection (MOI) of 50 up to 3.9-fold upon a 24-h incubation, to levels that approached those achieved at MOI of 200 for LV alone, in the presence or absence of the magnetic field. Magnetofection significantly increased the percentage of transduced cells up to 186-fold already after 15 min of incubation. In polarized cells, magnetofection increased GFP+ cells up to 24-fold compared to LV alone. Magnetofection did not enhance LDH release and slightly altered TER but not ZO-1 localization at the TJs. Conclusions: We conclude that magnetofection can facilitate in vitro LV-mediated transduction of airway epithelial cells, in the absence of overt cytotoxicity and maintaining epithelial integrity, by lowering the necessary vector dose and reducing the incubation time required to achieve efficient transduction. Copyright © 2010 John Wiley & Sons, Ltd.
Oz Biosciences | Date: 2015-10-14
Chemical products for use in industry, science, photography, as well as in agriculture, horticulture and forestry; chemical reagents other than for medical or veterinary use; biochemical, chemical and biological reagents for use in scientific research, in industry and science; chemical, biochemical and biological products for scientific, medical or pharmaceutical research. Pharmaceutical and veterinary products; sanitary products for medical purposes; dietetic food and substances for medical or veterinary use; food for babies; food supplements for humans and animals; materials for dressings; material for dental fillings and dental impressions; disinfectants; products for destroying vermin; fungicides, herbicides; bath preparations for medical use; sanitary panties or napkins; chemical preparations for medical or pharmaceutical use; medicinal herbs; herbal teas; parasiticides; alloys of precious metals for dental use; chemical, biochemical and biological products for medical or pharmaceutical use. Evaluations and assessments in the fields of science and technology provided by engineers; scientific and technical research; research and development of new products for others; technical project studies; scientific research for medical purposes; research and development of new products for applications in life sciences, in the pharmaceutical, parapharmaceutical and veterinary fields; research in biology, bacteriology, chemistry, cosmetology and physics.
Sapet C.,OZ Biosciences |
Pellegrino C.,French Institute of Health and Medical Research |
Laurent N.,OZ Biosciences |
Sicard F.,OZ Biosciences |
Zelphati O.,OZ Biosciences
Pharmaceutical Research | Year: 2012
Purpose: Adenoviruses are among the most powerful gene delivery systems. Even if they present low potential for oncogenesis, there is still a need for minimizing widespread delivery to avoid deleterious reactions. In this study, we investigated Magnetofection efficiency to concentrate and guide vectors for an improved targeted delivery. Method: Magnetic nanoparticles formulations were complexed to a replication defective Adenovirus and were used to transduce cells both in vitro and in vivo. A new integrated magnetic procedure for cell sorting and genetic modification (i-MICST) was also investigated. Results: Magnetic nanoparticles enhanced viral transduction efficiency and protein expression in a dose-dependent manner. They accelerated the transduction kinetics and allowed non-permissive cells infection. Magnetofection greatly improved adenovirus-mediated DNA delivery in vivo and provided a magnetic targeting. The i-MICSTresults established the efficiency of magnetic nanoparticles assisted viral transduction within cell sorting columns. Conclusion: The results showed that the combination of Magnetofection and Adenoviruses represents a promising strategy for gene therapy. Recently, a new integrated method to combine clinically approved magnetic cell isolation devices and genetic modification was developed. In this study, we validated that magnetic cell separation and adenoviral transduction can be accomplished in one reliable integrated and safe system. © Springer Science+Business Media, LLC 2011.
Oz Biosciences | Date: 2006-01-17
diagnostic preparations and reagents for scientific and medical research use; and chemical, biochemical and biological reagents for scientific and medical research use. diagnostic preparation and reagents for medicinal use; and chemical, biochemical and biological reagents for medicinal use. Research and development in the field of life sciences, pharmaceutical, parapharmaceutical and veterinary applications.