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unife
University of Ferrara
 
Presentation

Suitability for allocated work:
The Department of Experimental and Diagnostic Medicine and the Center of for Biothecnology - University of Ferrara, Italy - provides:
- full equipped laboratories;
- modern instrumentations to perform all the biochemical, biological, immunological and virological studies required to carry out the research program.
The Department and the Center are further equipped with two biosafety laboratories (P3) and with an animal facility.
Principal scientific and technical personnel involved:
Peggy Marconi, (Assistant professor),Virologist with a broad and international experience in HSV-1 vector development.
Rafaela Argnani, (Postdoc), extensive and international experience in constructing targetable HSV recombinant viruses.
Elena Berto, (Postdoc), long-term experience in developing replication-defective HSV-1 vectors.
Aleksandra Bozac, (Postdoc), research experience in the immunology of HSV-1 defective vectors.
Research fields:
- construction of defective recombinant vectors based on Herpes simplex type 1 virus for gene therapy;
- development of attenuated herpes simplex 1 vectors, engineered for specific binding to cell surface;
- development of chimeric vectors.
Contribution:
Construction and testing recombinant HSV-1 vectors expressing different transgenic functions conferring the vector anti-HCC activity, in collaboration
with P1 and P3.
 
Role in the project
OBJECTIVES
WP1. VECTORS:
The overall objective of this WP is to design, construct, and produce the whole set of vectors that will be used in this project. Our specific role is the following:
WP1.1 - Targeting virus multiplication to HCC cells.
1.1.1 Targeting liver cells at the level of entry of virus particles: Retargeting HSV-1 vectors at the level of entry by engineered HSV-1 vectors containing mutations in the envelope glycoproteins responsible for virus-cell interactions. P2 has recently modified mutant KgBp-gC- by substituting the HSPG domain of gC with a 27 amino acid active peptide. This peptide is part of the preS1 antigen of human hepatitis B virus (HBV) and it favours infection to hepatocytes by interacting with a specific cellular receptor.
WP1.2 - Enhancement of anti-tumour activity.
1.2.1 Inhibition of angiogenesis: The goal of this part of the project is to express transgenic proteins that can inhibit angiogenesis within the backbone
of targeted oncolytic vectors. We have recently developed two replication defective HSV-1 vectors were two transgenic cassettes, carrying endostatin::angiostatin or endostatin::kringle 5 fusion genes, acted synergically with a suicide gene approach in reducing the rate of tumour mass growth.
1.2.2 Inducing and/or increasing anti-tumour immune responses: a) immuno-modulatory molecules; b) tumour antigens.
1.2.3 Fusogenic properties.
Future perspectives
Elimination of residual gD binding to the cell surface either by: a) substitution with another fusogenic protein with any known binding activity (e.g. F glycoprotein of SV5 virus (Rubulavirus Simian parainfluenza virus); b) deletion of Hve A, B and C binding domains of gD (the resulting HSV-1 mutant can bind ONLY to hepatocytes).
Use of new HSV-1 fusogenic isolates to construct a HSV-1 fusogenic mutant that binds specifically to hepatocytes: in such mutant the transcription of essential gene/genes (e.g. gD and IE genes) will be driven by tumor specific promoters (e.g. MMP9), conferring tumor replication selectivity.
 
Scientific manager
Pr. Roberto Manservigi, (UFRA.SM.DMS), University of Ferrara, Italy, acts as Scientific manager and leader of WP1.
Qualifications: Current position (1994 -) Full Professor of Microbiology, University of Ferrara;
(2002 -) Head of the Department of Experimental and Diagnostic Medicine,
1990-1994: Representative of the University of Ferrara in the National Consortium of Biotechnology;
(1986-) Research leader and counsel member at the Interdepartmental Center for Biothecnology (CIBF), University of Ferrara; 1975-1977: Research Associate, University of Chicago, Chicago, USA (with Prof. PG Spear).
Capacity to provide contribution: Since 1989, project leader of molecular biology of HSV research group at CIBF, University of Ferrara. Management capabilities in National projects supported by the Ministry of University and Research (FIRB- development of vectors for human gene therapy;
PRIN-new vaccines based on viral vectors), the National Research Council (Biothecnology, Genetic Engineering, Clinical Application of Oncology Research), the National Institute of Health (AIDS project), by private foundations (Telethon-gene therapy project, AIRC-cancer gene therapy project) and in developing international collaboration with teams in France, Germany, Greece and USA. Member of the directory board of the National Society of Microbiology. Associated Editor for the International Journal Intervirology as an expert on Herpes simplex viruses and member of European and American Society of Gene Therapy. Reviewer of several scientific journals, including Gene Therapy and Human Gene Therapy. Former private consultant of Aviron Chiron Corporation-USA for problems related to the development of HSV-1 recombinant glycoproteins. His research group is associated to the National Inter-universities Consortium for Biotechnology (CIB) and the Department is considered a National Center of Excellence for scientific research.
Experience and knowledge contributed: Construction of defective recombinant vectors based on herpes simplex type 1 virus for the gene therapy of the central nervous system. Development of attenuated herpes simplex 1 vectors, engineered for specific binding to cell surface and of chimeric vectors.
 
Contact

Pr. Roberto MANSERVIGI
Phone:+39 0532291401
Fax:+39 0532247618
mns(at)unife.it

 Università degli Studi di Ferrara
Pr. Roberto MANSERVIGI
Via Luigi Borsari n° 46
44100 Ferrara
Italy
http://www.unife.it