Alberto Auricchio – FTELE.IGM Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy Fondazione Telethon, Rome, Italy

Institute description
The Telethon Institute of Genetics and Medicine (TIGEM) is part of a science and technology research complex that is also home to the CNR’s Institutes of Genetics and Biophysics (IGB) and of Protein Biochemistry (IBP). The Institute comprises 13 independent research groups with over 170 members including graduate students, post-doc fellows, technicians and administration. Research at TIGEM focuses on the study of rare diseases. Research approaches include cell biology, functional genomics, systems biology and gene therapy. Research activity at TIGEM is supported by several core facilities (AAV vector Core, Microscopy and Imaging Core, Cell Culture and Cytogenetics Core, Behavioural Core, Transgenic and Knock-out Core Facility, Bioinformatics Core) that provide state-of-the art technology as well as “house-keeping” assistance. The Institute is fully equipped to perform molecular and cellular biology experiments. An animal facility (600 sqm) is located on the ground floor of the laboratory building. TIGEM (together with the Fondazione Telethon) is responsible for the financial administration of the project.

Group leader
Alberto Auricchio, MD, is Associate Professor of Medical Genetics at the Federico II University of Naples and is Principal Investigator at TIGEM. He is board-certified in Pediatrics. In addition to his research activities, Prof. Auricchio supervises the TIGEM adeno-associated virus (AAV) vector Core providing research-grade AAV vector preps to TIGEM scientists and external collaborators.

Prof. Auricchio has pioneered the use of AAV serotypes for gene transfer to the retina and other tissues, as well as their use for treatment of animal models of retinal and metabolic diseases.

He observed that the different ability of AAV vectors to efficiently transduce target tissues like the lung or retina in vivo depends on the composition of AAV capsid proteins, which differ from one AAV serotype to the other and can be easily interchanged among various serotype vectors. Building on this observation, Prof. Auricchio exploited the AAV capsid interaction with specific receptors to design protocols for affinity purification of AAV vectors with high titers and purity. Based on the various tropism of different AAV serotypes, he applied AAV-mediated gene transfer to a variety of models of retinal and metabolic diseases.

Moreover, in collaboration with the Department of Ophthalmology of the Second University of Naples, Prof. Auricchio has contributed to the molecular and clinical characterization of a series of patients with Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA) allowing the selection of candidates for gene therapy clinical trials.

Role in the project
Coordinator for the grant, Workpackage Leader for WP1 and WP5, and Chair of the Plenary Meeting. His laboratory is involved in all the workpackages (WP1-WP5) of the proposal and, in particular, in i. developing and testing AAV vectors for optimal photoreceptor gene transfer for Aipl1 deficiency (WP1); ii. testing AAV-mediated gene replacement in the rd10 and Aipl1 -/- murine models (WP2); iii. testing the therapeutic synergistic effect of Ca++ -channel blockers and gene replacement in models of Pde6b and Aipl1 deficiencies (WP3), and iv. characterizing RP and LCA Italian patients at the clinical and molecular level (WP4).

Key personnel

Key publications

Colella P, Cotugno G, Auricchio A (2009). Ocular gene therapy: current progress and future prospects. Trends Mol Med 15: 23-31.

Allocca M, Doria M, Petrillo M, Colella P, Garcia-Hoyos M, Gibbs D, Kim SR, Maguire A, Rex TS, Di Vicino U, Cutillo L, Sparrow JR, Williams DS, Bennett J, Auricchio A (2008). Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective in vivo gene delivery in mice. J Clin Invest 118: 1955-1964.

Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr., Mingozzi F, Bennicelli J, Banfi S, Marshall KA, Testa F, Surace EM, Rossi S, Lyubarsky A, Arruda VR, Konkle B, Stone E, Sun J, Jacobs J, Dell’osso L, Hertle R, Ma JX, Redmond TM, Zhu X, Hauck B, Zelenaia O, Shindler KS, Maguire MG, Wright JF, Volpe NJ, McDonnell JW, Auricchio A, High KA, Bennett J (2008). Safety and efficacy of gene transfer for Leber’s Congenital Amaurosis. N Engl J Med 358: 2240-2248.

Tessitore A, Faella A, O’Malley T, Cotugno G, Doria M, Kunieda T, Matarese G, Haskins M, Auricchio A (2008). Biochemical, pathological and skeletal improvement of Mucopolysaccharidosis VI after gene transfer to liver but not to muscle. Mol Ther 16: 30-37.

Allocca M, Mussolino C, Garcia-Hoyos M, Sanges D, Iodice C, Petrillo M, Vandenberghe LH, Wilson JM, Marigo V, Surace EM, Auricchio A (2007). Novel adeno-associated virus serotypes efficiently transduce murine photoreceptors. J Virol 81: 11372-11380.