Serena Zacchigna

Group Leader
Cardiovascular Biology
International Centre for Genetic Engineering and Biotechnology
Padriciano 99
34149 Trieste, Italy
Tel: +39-040-3757354/214


Faculty of Medicine, University of Trieste, Italy, MD, 2000
Admitted to the Medical Doctors and Surgeons Register, 2001
International School for Advanced Studies (ISAS), Trieste, Italy, PhD, 2005

Career History

Since January 2015, Group Leader, Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology, ICGEB, Trieste, Italy Currently on Special Leave
2007-2014, Staff Scientist, Molecular Medicine Laboratory, ICGEB Trieste, Italy.
2006-2007, Postdoctoral Fellow (Marie Curie EIF), Center for Transgene Technology & Gene Therapy, Flanders Interuniversity Institute for Biotechnology (VIB)/KU Leuven, Belgium.
2001-2005, PhD Student at the ISAS/ICGEB Trieste, Italy.
1994-2000, Pre-doctoral student and fellow at ICGEB, Trieste, Italy.

Scientific Activity

Main research interests focus on the understanding of the cellular and molecular interactions controlling vessel formation and tissue growth in development and disease, with special attention to the cross-talk between endothelial cells, immune cells, mesenchymal stromal cells, cancer cells and cardiomyocytes. The overall goal of current research activity is to develop novel therapeutic approaches for tissue revascularization and cancer. Past research interests have focused on the use of AAV vectors and synthetic miRNAs to induce angiogenesis and cardiac regeneration, as well as on role of angiogenic factors in neuronal and retina degeneration. S. Zacchigna also works in close collaboration with the clinical and industrial sector to understand the mechanism of action and optimize clinical protocols of low-power laser therapy.

She regularly reviews scientific manuscripts for international journals in the fields of cardiac development, angiogenesis, cancer and cardiovascular disorders, and presents her research results at national and international meetings. She has published over 50 papers in peer-reviewed international journals and 10 invited reviews or chapters in published books and university text books.

Teaching Activity

Since 2008, Lecturer, PhD Courses at ICGEB and University of Nova Gorica, Italy.
Since 2006, Supervisor, PhD students at KU Leuven, University of Trieste and ICGEB.
Since 2001, External Professor, course in Gene Therapy and Stem Cells, Medical School, University of Trieste.

Selected publications

Zacchigna S on PubMed

Kazemi, M., Carrer, A., Moimas S., Zandonà L., Bussani R., Casagrande B., Palmisano S., Prelazzi P., Giacca M., Zentilin L., De Manzini, N., Giacca M., Zacchigna S. 2016. VEGF121 and VEGF165 differentially promote vessel maturation and tumor growth in mice and humans. Cancer Gene Therapy 23(5):125-32. PubMed link

Ottaviani, G., Martinelli, V., Rupel, K., Caronni, N., Naseem, A., Zandonà L., Perinetti, G., Gobbo, M., Di Lenarda, R., Bussani, R., Benvenuti, F., Giacca, M., Biasotto, M., Zacchigna, S. 2016. Laser Therapy Inhibits Tumor Growth in Mice by Promoting Immune Surveillance and Vessel Normalization. EBioMedicine. Jul 25. pii: S2352-3964(16)30340-1. PubMed link

Zanotti, L., Angioni, R., Calì, B., Soldani, C., Ploia, C., Moalli, F., Gargesha, M., D’Amico, G., Elliman, S, Tedeschi, G., Maffioli, E., Negri, A., Zacchigna, S., Sarukhan, A., Stein, J.V., Viola, A. 2016. Mouse mesenchymal stem cells inhibit high endothelial cell activation and lymphocyte homing to lymph nodes by releasing TIMP-1. Leukemia.  22. doi: 10.1038/leu.2016.33. PubMed link

Giacca, M., Zacchigna, S. 2015. Harnessing the microRNA pathway for cardiac regeneration. J Mol Cell Cardiol. Dec;89(Pt A):68-74. PubMed link

Mano, M., Ippodrino, R., Zentilin, L., Zacchigna, S., Giacca, M. 2015. Genome-wide RNAi screening identifies host restriction factors critical for in vivo AAV transduction. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11276-81. PubMed link

Ruozi, G., Bortolotti, F., Falcione, A., Dal Ferro, M., Ukovich, L., Macedo, A., Zentilin, L., Filigheddu, N., Gortan Cappellari, G., Baldini, G., Zweyer, M., Barazzoni, R., Graziani, A., Zacchigna ,S., Giacca, M. 2015. AAV-mediated in vivo functional selection identifies ghrelin as an inducer of myoprotective autophagy. Nat Commun. 11;6:7388. PubMed link

Bortolotti, F., Ukovich, L., Razban, V., Martinelli, V., Ruozi, G., Pelos, B., Dore F., Giacca, M., Zacchigna, S. In vivo therapeutic potential of mesenchymal stromal cells depends on source and isolation procedure. Stem Cell Reports 2015, in press

Aguirre A, Montserrat N, Zacchigna S, Nivet E, Hishida T, Krause MN, Kurian L, Ocampo A, Vazquez-Ferrer E, Rodriguez-Esteban C, Kumar S, Moresco JJ, Yates JR 3rd, Campistol JM, Sancho-Martinez I, Giacca M, Izpisua Belmonte JC. In vivo activation of a conserved microRNA program induces mammalian heart regeneration. Cell Stem Cell. 2014 Nov 6;15(5):589-604

Moser DA, Braga L, Raso A, Zacchigna S, Giacca M, Simon P. Transgene detection by digital droplet PCR. PLoS One. 2014 Nov 6;9(11):e111781

Felician G, Collesi C, Lusic M, Martinelli V, Ferro MD, Zentilin L, Zacchigna S, Giacca M. Epigenetic modification at notch responsive promoters blunts efficacy of inducing notch pathway reactivation after myocardial infarction. Circ Res. 2014 Sep 12;115(7):636-49.

Zacchigna S, Zentilin L, Giacca M. Adeno-associated virus vectors as therapeutic and investigational tools in the cardiovascular system. Circ Res. 2014 May 23;114(11):1827-46

Puente BN, Kimura W, Muralidhar SA, Moon J, Amatruda JF, Phelps KL, Grinsfelder D, Rothermel BA, Chen R, Garcia JA, Santos CX, Thet S, Mori E, Kinter MT, Rindler PM, Zacchigna S, Mukherjee S, Chen DJ, Mahmoud AI, Giacca M, Rabinovitch PS, Aroumougame A, Shah AM, Szweda LI, Sadek HA. The oxygen-rich postnatal environment induces cardiomyocyte cell-cycle arrest through DNA damage response. Cell. 2014 Apr 24;157(3):565-79.

Zacchigna S, Giacca M. Extra- and intracellular factors regulating cardiomyocyte proliferation in postnatal life. Cardiovasc Res. 2014 May 1;102(2):312-20.

Gobbo M, Ottaviani G, Perinetti G, Ciriello F, Beorchia A, Giacca M, Di Lenarda R, Rupel K, Tirelli G, Zacchigna S, Biasotto M. Evaluation of nutritional status in head and neck radio-treated patients affected by oral mucositis: efficacy of class IV laser therapy. Support Care Cancer. 2014 Jul;22(7):1851-6

Chermetz M, Gobbo M, Ronfani L, Ottaviani G, Zanazzo GA, Verzegnassi F, Treister NS, Di Lenarda R, Biasotto M, Zacchigna S. Class IV laser therapy as treatment for chemotherapy-induced oral mucositis in onco-haematological paediatric patients: a prospective study. Int J Paediatr Dent. 2013 Dec 25. doi: 10.1111/ipd.12090. [Epub ahead of print]

Kleiner G, Celsi F, Tricarico PM, Zacchigna S, Crovella S, Marcuzzi A. Systemic and neuronal inflammatory markers in a mouse model of mevalonate kinase deficiency: a strain-comparative study. In Vivo. 2013 Nov-Dec;27(6):715-22.

Ottaviani G, Gobbo M, Sturnega M, Martinelli V, Mano M, Zanconati F, Bussani R, Perinetti G, Long CS, Di Lenarda R, Giacca M, Biasotto M, Zacchigna S. Effect of class IV laser therapy on chemotherapy-induced oral mucositis: a clinical and experimental study. Am J Pathol. 2013 Dec;183(6):1747-57

Zanin V, Marcuzzi A, Kleiner G, Piscianz E, Monasta L, Zacchigna S, Crovella S, Zauli G. Lovastatin Dose-Dependently Potentiates the Pro-inflammatory Activity of Lipopolysaccharide Both In Vitro and In Vivo. J Cardiovasc Transl Res. 2013 Dec;6(6):981-8.

Heymans S, Corsten MF, Verhesen W, Carai P, van Leeuwen RE, Custers K, Peters T, Hazebroek M, Stöger L, Wijnands E, Janssen BJ, Creemers EE, Pinto YM, Grimm D, Schürmann N, Vigorito E, Thum T, Stassen F, Yin X, Mayr M, De Windt LJ, Lutgens E, Wouters K, de Winther MP, Zacchigna S, Giacca M, van Bilsen M, Papageorgiou AP, Schroen B. Macrophage MicroRNA-155 Promotes Cardiac Hypertrophy and Failure. Circulation. 2013 Sep 24;128(13):1420-32

Moimas S, Novati F, Ronchi G, Zacchigna S, Fregnan F, Zentilin L, Papa G, Giacca M, Geuna S, Perroteau I, Arnež ZM, Raimondo S. Effect of vascular endothelial growth factor gene therapy on post-traumatic peripheral nerve regeneration and denervation-related muscle atrophy. Gene Ther. 2013 Oct;20(10):1014-21

Bono F, De Smet F, Herbert C, De Bock K, Georgiadou M, Fons P, Tjwa M, Alcouffe C, Ny A, Bianciotto M, Jonckx B, Murakami M, Lanahan AA, Michielsen C, Sibrac D, Dol-Gleizes F, Mazzone M, Zacchigna S, Herault JP, Fischer C, Rigon P, Ruiz de Almodovar C, Claes F, Blanc I, Poesen K, Zhang J, Segura I, Gueguen G, Bordes MF, Lambrechts D, Broussy R, van de Wouwer M, Michaux C, Shimada T, Jean I, Blacher S, Noel A, Motte P, Rom E, Rakic JM, Katsuma S, Schaeffer P, Yayon A, Van Schepdael A, Schwalbe H, Gervasio FL, Carmeliet G, Rozensky J, Dewerchin M, Simons M, Christopoulos A, Herbert JM, Carmeliet P. Inhibition of tumor angiogenesis and growth by a small-molecule multi-FGF receptor blocker with allosteric properties. Cancer Cell. 2013 Apr 15;23(4):477-88

Eulalio A, Mano M, Ferro MD, Zentilin L, Sinagra G, Zacchigna S, Giacca M. Functional screening identifies miRNAs inducing cardiac regeneration. Nature. 2012 Dec 20;492(7429):376-81.

Carrer A, Moimas S, Zacchigna S, Pattarini L, Zentilin L, Ruozi G, Mano M, Sinigaglia M, Maione F, Serini G, Giraudo E, Bussolino F, Giacca M. Neuropilin-1 Identifies a Subset of Bone Marrow Gr1- Monocytes That Can Induce Tumor Vessel Normalization and Inhibit Tumor Growth. Cancer Res. 2012 Dec 7.

Moimas S, Zacchigna S, Merlo M, Buiatti A, Anzini M, Dreas L, Salvi A, Di Lenarda A, Giacca M, Sinagra G. Idiopathic dilated cardiomyopathy and persistent viral infection: Lack of association in a controlled study using a quantitative assay. Heart Lung Circ. 2012 Aug 14.

Lovric J, Mano M, Zentilin L, Eulalio A, Zacchigna S, Giacca M. Terminal Differentiation of Cardiac and Skeletal Myocytes Induces Permissivity to AAV Transduction by Relieving Inhibition Imposed by DNA Damage Response Proteins. Mol Ther. 2012 Jul 31

Giacca M, Zacchigna S. Virus-mediated gene delivery for human gene therapy. J Control Release. 2012 Jul 20;161(2):377-88. Epub 2012 Apr 10

Giacca M, Zacchigna S. VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond. Gene Ther. 2012 Mar 1. doi: 10.1038/gt.2012.17.

Macedo A, Moriggi M, Vasso M, De Palma S, Sturnega M, Friso G, Gelfi C, Giacca M, Zacchigna S. Enhanced athletic performance on multisite AAV-IGF1 gene transfer coincides with massive modification of the muscle proteome. Hum Gene Ther. 2012 Feb;23(2):146-57.

Zhong,X., Huang, H., Shen,J., Zacchigna, S., Zentilin, L., Giacca, M., Vinores, S.A., Vascular endothelial growth factor-B gene transfer exacerbates retinal and choroidal neovascularization and vasopermeability without promoting inflammation. Molecular Vision 2011; 17:492-507.

Toffoli B, Bernardi S, Candido R, Zacchigna S, Fabris B, Secchiero P. TRAIL shows potential cardioprotective activity. Invest New Drugs. 2011 Jan 4.

Ruiz de Almodovar C, Coulon C, Salin PA, Knevels E, Chounlamountri N, Poesen K, Hermans K, Lambrechts D, Van Geyte K, Dhondt J, Dresselaers T, Renaud J, Aragones J, Zacchigna S, Geudens I, Gall D, Stroobants S, Mutin M, Dassonville K, Storkebaum E, Jordan BF, Eriksson U, Moons L, D’Hooge R, Haigh JJ, Belin MF, Schiffmann S, Van Hecke P, Gallez B, Vinckier S, Chédotal A, Honnorat J, Thomasset N, Carmeliet P, Meissirel C. Matrix-binding vascular endothelial growth factor (VEGF) isoforms guide granule cell migration in the cerebellum via VEGF receptor Flk1. J Neurosci. 2010 Nov 10;30(45):15052-66

Storkebaum E, Ruiz de Almodovar C, Meens M, Zacchigna S, Mazzone M, Vanhoutte G, Vinckier S, Miskiewicz K, Poesen K, Lambrechts D, Janssen GM, Fazzi GE, Verstreken P, Haigh J, Schiffers PM, Rohrer H, Van der Linden A, De Mey JG, Carmeliet P. Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation. 2010 Jul 20;122(3):273-81.

Pepe M, Mamdani M, Zentilin L, Csiszar A, Qanud K, Zacchigna S, Ungvari Z, Puligadda U, Moimas S, Xu X, Edwards JG, Hintze TH, Giacca M, Recchia FA. Intramyocardial VEGF-B167 Gene Delivery Delays the Progression Towards Congestive Failure in Dogs With Pacing-Induced Dilated Cardiomyopathy. Circ Res. 2010 Jun 25;106(12):1893-903

Van de Veire S, Stalmans I, Heindryckx F, Oura H, Tijeras-Raballand A, Schmidt T, Loges S, Albrecht I, Jonckx B, Vinckier S, Van Steenkiste C, Tugues S, Rolny C, De Mol M, Dettori D, Hainaud P, Coenegrachts L, Contreres JO, Van Bergen T, Cuervo H, Xiao WH, Le Henaff C, Buysschaert I, Kharabi Masouleh B, Geerts A, Schomber T, Bonnin P, Lambert V, Haustraete J, Zacchigna S, Rakic JM, Jiménez W, Noël A, Giacca M, Colle I, Foidart JM, Tobelem G, Morales-Ruiz M, Vilar J, Maxwell P, Vinores SA, Carmeliet G, Dewerchin M, Claesson-Welsh L, Dupuy E, Van Vlierberghe H, Christofori G, Mazzone M, Detmar M, Collen D, Carmeliet P. Further pharmacological and genetic evidence for the efficacy of PlGF inhibition in cancer and eye disease. Cell. 2010 Apr 2;141(1):178-90.

Biasotto M, Chiandussi S, Zacchigna S, Moimas S, Dore F, Pozzato G, Cavalli F, Zanconati F, Contardo L, Giacca M, Di Lenarda R. A novel animal model to study non-spontaneous bisphosphonates osteonecrosis of jaw. J Oral Pathol Med. 2010 May;39(5):390-6.

Zentilin L, Puligadda U, Lionetti V, Zacchigna S., Collesi C, Pattarini L, Ruozi G, Camporesi S, Sinagra G, Pepe M, Recchia FA, Giacca M. Cardiomyocyte VEGFR-1 activation by VEGF-B induces compensatory hypertrophy and preserves cardiac function after myocardial infarction. FASEB J. 2010 May;24(5):1467-78.

Tafuro S., Ayuso E., Zacchigna S., Zentilin L,. Moimas S., Dore F., Giacca M. Inducible AAV vectors induce functional angiogenesis in adult organisms via regulated VEGF expression. Cardiovasc Res 2009 Sep 1;83(4):663-71

Zacchigna S., Oh H., Wilsch-Bräuninger M., Missol-Kolka E., Jászai J., Jansen S., Tanimoto N., Tonagel F., Seeliger M., Huttner WB., Corbeil D., Dewerchin M., Vinckier S., Moons L., Carmeliet P. Loss of the Cholesterol-Binding Protein Prominin-1/CD133 Causes Disk Dysmorphogenesis and Photoreceptor Degeneration. J Neurosci 2009 Feb18; 29(7):2297-2308

Fiotti, N., Altamura, N., Moretti, M., Wassermann, S., Zacchigna, S., Farra, R., Dapas, B., Consoloni, L., Giacca, M., Grassi, G., Giansante, C. Short Term Effects of Doxycycline on Matrix Metalloproteinases 2 and 9. Cardiovasc Drugs Ther 2008, Dec 4

Zacchigna S., Pattarini L., Zentilin L., Moimas S., Carrer A., Sinigaglia M., Arsic N., Tafuro S., Sinagra G., Giacca M. Bone marrow cells recruited through the neuropilin-1 receptor promote arterial formation at the sites of adult neoangiogenesis in mice. J Clin Invest. 2008, 118(6):2062-75.

Zacchigna, S., Lambrechts, D., Carmeliet, P. Neurovascular signaling defects in neurodegeneration. Nature Review Neuroscience 2008, 9(3):169-81.

Aragones, J., Schneider, M., van Geyte, K., Freisl, P., Dresselaers, T., Mazzone, M., Dirx, R., Zacchigna, S., Lemieux, H., Jeoung, N.H., Lambrechts, D., Bishop, T., Lafuste, P., Diez-Juan, A., Harten, S.K., Van Noten, P., De Bock K., William, C., Tjwa, Grosfeld, A., M, Navet, R., Moons, L., Vandendriessche, T., Deroose, C., Wijeyekoon, B., Nuyts, J., Jordan, B., Silasi-Mansat, R., Lupu, F., Dewerchin, M., Pugh C., Salmon, P., Mortelmans L., Gallez, B., Gorus, F., Buyse, J., Harris, R.A., Gnaiger, E., Hespel, P., Van Hecke P., Schuit, F., Van Veldhoven, P., Ratcliffe P., Baes, M., Maxwell, P., Carmeliet, P. Loss of the oxygen sensor PHD1, but not PHD2 or PHD3, protects ischemic skeletal muscle against oxidative damage. Nature Genetics 2008, 40(2):170-80

Wei, C., Moller, C., Altintas, M., Li, J., Schwartz, K., Zacchigna, S., Xie, L., Henger, A., Schmid, H., Rastaldi, M.P., Cowan, P., Kretzler, M., Parrilla, R., Bendayan, Gupta, V., M., Nikolic, B., Kalluri, R., Carmeliet, P., Mundel, P., Reiser, J. Modification of kidney barrier function by the urokinase receptor. Nature Medicine 2008, 14:55-63

Zacchigna, S., Østli, EK., Arisc. N.,Pattarini, L., Giacca, M., Djurovic, S. A novel myogenic cell line with phenotypic properties of muscle progenitors. Journal of Molecular Medicine 2008, 86(1):105-15.

Carrer, A., Zacchigna, S., Balani, A., Pistan, V., Adami, A., Porcelli, F., Scaramucci, M., Roteano, M., Turoldo, A., Prati, MC., Dell’omodarme, M., DeManzini, N., Giacca, M. Expression profiling of angiogenic genes for the characterisation of colorectal carcinoma. Eur J Cancer 2008; 44(12):1761-9

Zago P., Baralle M., Ayala Y.M., Skoko N., Zacchigna S., Buratti E., Tisminetzky S. Improving human beta interferon production in mammalian cell lines by insertion of an intronic sequence within its naturally uninterrupted gene. Biotechnol Appl Biochem. 2009; 52:191-198

Fischer, C., Jonckx, B., Mazzone, M., Zacchigna, S., Loges, S., Pattarini, L., Chorianopoulos, E., Liesenborghs, L., Koch, M., Demol, M., Wyns, S., Autiero, M., Plaisance, S., Moons, L., van Rooijen, N., Giacca, M., Stassen, J., Dewerchin, M., Collen, D.; Carmeliet, P. A monoclonal anti-PlGF antibody inhibits tumor growth and lymphatic metastasis without affecting healthy vessels. Cell 2007; 131(3):463-75.

Zacchigna S, Tasciotti E, Kusmic C, Arsic N, Sorace O, Marini C, Marzullo P, Pardini S, Petroni D, Pattarini L, Moimas S, Giacca M, Sambuceti G. In Vivo Imaging Shows Abnormal Function of Vascular Endothelial Growth Factor-Induced Vasculature. Human Gene Therapy 2007;18(6):515-24.

Antonini A., Zacchigna S., Papa G., Novati F., Pascone M., Giacca M. Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer. Microsurgery. 2007;27(5):439-45.

Zentilin L, Tafuro S, Zacchigna S, Arsic N, Pattarini L, Sinigaglia M, Giacca M. Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels. Blood 2006;107(9):3546-54.

Secchiero P, Candido R, Corallini F, Zacchigna S, Toffoli B, Rimondi E, Fabris B, Giacca M, Zauli G. Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows antiatherosclerotic activity in apolipoprotein E-null diabetic mice. Circulation 2006;114(14):1522-30.

Ferrarini M, Arsic N, Recchia FA, Zentilin L, Zacchigna S, Xu X, Linke A, Giacca M, Hintze TH. Adeno-associated virus-mediated transduction of VEGF165 improves cardiac tissue viability and functional recovery after permanent coronary occlusion in conscious dogs. Circ Res 2006;98(7):954-61.

Zacchigna S, Papa G, Antonini A, Novati F, Moimas S, Carrer A, Arsic N, Zentilin L, Visintini V, Pascone M, Giacca M. Improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors. Am J Pathol 2005;167(4):981-91.

Camozzi M, Zacchigna S, Rusnati M, Coltrini D, Ramirez-Correa G, Bottazzi B, Mantovani A, Giacca M, Presta M. Pentraxin 3 inhibits fibroblast growth factor 2-dependent activation of smooth muscle cells in vitro and neointima formation in vivo. Arterioscler Thromb Vasc Biol 2005;25(9):1837-42.

Zacchigna S, Zentilin L, Morini M, Dell’Eva R, Noonan DM, Albini A, Giacca M. AAV-mediated gene transfer of tissue inhibitor of metalloproteinases-1 inhibits vascular tumor growth and angiogenesis in vivo. Cancer Gene Ther 2004;11(1):73-80.

Secchiero P, Gonelli A, Carnevale E, Corallini F, Rizzardi C, Zacchigna S, Melato M, Zauli G. Evidence for a proangiogenic activity of TNF-related apoptosis-inducing ligand. Neoplasia 2004;6(4):364-73.

Ramirez Correa GA, Zacchigna S, Arsic N, Zentilin L, Salvi A, Sinagra G, Giacca M. Potent inhibition of arterial intimal hyperplasia by TIMP1 gene transfer using AAV vectors. Mol Ther 2004;9(6):876-84.

Arsic N, Zacchigna S, Zentilin L, Ramirez-Correa G, Pattarini L, Salvi A, Sinagra G, Giacca M. Vascular endothelial growth factor stimulates skeletal muscle regeneration in vivo. Mol Ther 2004;10(5):844-54.

Arsic N, Zentilin L, Zacchigna S, Santoro D, Stanta G, Salvi A, Sinagra G, Giacca M. Induction of functional neovascularization by combined VEGF and angiopoietin-1 gene transfer using AAV vectors. Mol Ther 2003;7(4):450-9.