2019 Prize Winner

Professor Alberto Auricchio’s research project on Gene therapy of Stargardt disease with AAV intein vectors was chosen as the winner of the € 100,00 Arrigo Recordati Prize 2019. Alberto Auricchio, MD is Professor of Medical Genetics at the Department of Advanced Biomedicine, “Federico II” University in Naples, and Coordinator of the Molecular Therapy Program at Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli (Naples), Italy. His research is focused on gene therapy of retinal and metabolic diseases using adeno- associated viral vectors.



Alberto Auricchio

Alberto Auricchio, M.D.
Telethon Institute of Genetics and Medicine
(TIGEM), Naples, Italy

2019 Award Winner

Alberto Auricchio, MD is Professor of Medical Genetics at the Department of Advanced Biomedicine, “Federico II” University in Naples, and Coordinator of the Molecular Therapy Program at Telethon Institute of Genetics and Medicine (TIGEM) in Pozzuoli (Naples), Italy. His research is focused on gene therapy of retinal and metabolic diseases using adeno-associated viral vectors. His group has contributed to the phase I/II clinical trial of Luxturna, the first approved gene therapy drug for an ocular disease, and to the development of gene therapy for mucopolysaccharidosis VI up to an ongoing phase  I/II trial.

Professor Auricchio is co-author of more than 130 peer-reviewed publications on international scientific journals and inventor of several international patents on the use of viral vectors for gene therapy. He is a member of the editorial boards of various journals and of the European Society of Cell and Gene Therapy.

In 2006 Professor Auricchio received the Outstanding New Investigator Award from the American Society of Gene Therapy and in 2007 was nominated “Cavaliere of the Italian Republic” by the President of the Italian Republic. In 2011 Professor Auricchio received the Consolidator Grant from the European Research Council - ERC - and the Advanced Grant in 2016.


  
Gene Therapy

Gene therapy of Stargardt disease
with AAV intein vectors
Alberto Auricchio, M.D.
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy

Our group has a long-standing interest in the development of gene therapies for inherited ocular diseases. Our research spans from tailoring the adeno-associated viral (AAV) vector platform to retinal gene transfer to proof-of-concept in animal models of retinal disease up to first-in-human. Indeed, we have importantly contributed to the phase I/II clinical trial of Luxturna, which is the first ocular gene therapy product on the market.

One of the limitations of AAV is its DNA cargo capacity of about 5 kb in size. This would not be sufficient for gene therapy of conditions like Stargardt disease (STGD1), the most common inherited macular degeneration in humans, which is caused by mutations in ABCA4, a gene with a coding sequence significantly larger than 5 kb.

To overcome this, we have recently developed a system based on two AAV vectors, each encoding for one of the two halves of ABCA4 each flanked by short split-inteins which mediate protein trans-splicing and full length ABCA4 reconstitution in the retina of mice, pigs and in human retinal organoids. This system reduces lipofuscin accumulation in a mouse model of STGD1 and supports further development of AAV intein for therapy  of STGD1 and other Inherited Retinal Diseases (IRDs) due to mutations in large genes.

The overall objective of the project funded by Arrigo Recordati International Prize for Scientific Research is to translate this proof-of-concept of pre-clinical efficacy of AAV split intein for STGD1 into a first-in-humans by defining both AAV intein dose-response and safety in view of a future clinical trial. This will importantly contribute to the development of gene therapy for the common and severe STGD1.