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Cell and gene therapy Print E-mail


Incorporation of fluorescently labeled LDL in LDLR-deficient cells
Incorporation of fluorescently labeled LDL in LDLR-deficient cells treated with an adenoviral vector expressing LDLR


Lipid staining of aortas from ApoE-deficient mice treated with either a helper-dependent adenoviral vector expressing apolipoprotein A-I (+) or with a control vector (-) on high-fat and regular diet
Lipid staining of aortas from ApoE-deficient mice treated with either a helper-dependent adenoviral vector expressing apolipoprotein A-I (+) or with a control vector (-) on high-fat and regular diet. Treated mice show reduced intimal fat deposition compared to control mice


Our research activity is broadly focused on gene and cell therapy. Gene therapy is aimed at introducing a transgene into a cell, tissue or organism in order to replace a defective gene, enhance a cell function or inhibit the expression of selected proteins. We are investigating the possibility of correcting the genetic defect in several inborn errors of metabolism, including familial hypercholesterolemia (FH) and phenylketonuria (PKU). A fundamental feature of gene therapy research is the proof of concept of the strategy in the animal model of the disease, and the assessment of toxicity in model organisms such as mice and nonhuman primates. We have been able to correct the defect in FH in animal models and to obtain a chemically-modified version of our vectors (PEGylated helperdependent adenoviral vectors) that substantially abrogates the main adenoviral toxicity, thereby allowing clinical use. We are currently investigating the possibility of producing our gene transfer vectors according to the Good Manufacturing Procedures (GMP) standards, which is necessary for human applications. To this aim, a GMP facility is under construction and the methodologies are being developed. The gene and cell therapy laboratory also studies regenerative medicine. The discovery of stem cells in both embryonic and adult tissues and the ability of these cells to differentiate towards different cell types and tissues after appropriate stimuli led to the possibility of regenerating tissues damaged by pathological conditions. Recent clinical applications involve myocardial, corneal and epidermal regeneration. We are currently investigating bone and myocardial regeneration in animal models using bone marrow stromal cells seeded on appropriate polymeric scaffolds and stimulated with growth factors that induce differentiation towards the desired tissues. We are testing the efficacy and toxicity of our procedures on mouse, rat and rabbit models in order to transfer our research results into clinical applications by means of GMPquality isolation, characterization and transduction of adult stem cells. Our lines of research can be broadly considered translational medicine and the main objectives consist in transferring basic science observations into innovative therapies and testing them in clinical trials.


PRINCIPAL INVESTIGATOR
Pastore Lucio

TEAM
Astone Dalila (dottoranda)
Cantilena Bruno (dottorando SEMM)
Castanò Ilenia (dottoranda)
Cerreto Monica (dottoranda SEMM)
Cozzolino Carmine (dottorando)
Esposito Maria Teresa (dottoranda SEMM)
Leggiero Eleonora (dottoranda)
Lombardo Barbara (formanda Ceinge)
Parisi Silvia (formanda Ceinge)

RESEARCH LINES 

BIBLIOGRAPHY

  • Croyle M. A., Hong Le, Linse K., Xin Ming, Cerullo V., Toietta G., Beaudet A., Pastore L.
    PEGylated Helper-Dependent Adenoviral Vectors: Highly Efficient Vectors with an Enhanced Safety Profile.
    Gen Ther 2005; 12(7):579-87.

  • Frisso G., Sampaolo S., Pastore L., Carlomagno A., Calise R. M., Di Iorio G., and Salvatore F.
    Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy.
    Neur Musc Dis 2002; 12(5):494-497.

  • Iaccarino G., Ciccarelli M., Cipolletta E., Sorriento D., Cerullo V., Annechiarico M., Iovino G.L., Paudice A., Elia A., Arcucci O., Pastore L., Salvatore F., Condorelli G., Trimarco B.
    AKT participates in endothelial dysfunction in hypertension.
    Circulation 2004; 109(21):2587-93.

  • Iaccarino G., Ciccarelli M., Sorriento D., Galasso G., Cerullo V., Aorta V., Cimini V., Piscione F., Pastore L., Salvatore F., Koch W. J., Trimarco B.
    Ischemic neoangiogenesis enhanced by b2-adrenergic receptor overexpression: A novel role for the endothelial adrenergic system.
    Circ Res 2005; 97(11):1182-9.

  • Toietta G., Pastore L., Cerullo V., Finegold M., Beaudet A.L., Lee B.
    Generation of helper-dependent adenoviral vectors by homologous recombination.
    Mol Ther 2002; 5 (2): 204-210.
 
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