Alessandra Biffi MD

Alessandra Biffi, MD

Director, Gene Therapy Program

Associate Professor of Pediatrics, Harvard Medical School

  • Contact: 617-632-2204

Medical Services

Specialties

  • Gene Therapy
  • Metabolic Disorders
  • Lysosomal Disorders
  • Hematopoietic Stem Cell Transplantation

Departments

  • Hematology / Oncology
To schedule an appointment: Call 617-632-2204 or Request an Appointment

Experience and Education

Education

Medical School

University of Milano School of Medicine and San Raffaele Institute, 1998

Milano, Italy

Fellowship

University of Milano School of Medicine and San Raffaele Institute, 1998

Milano, Italy

Internship

University of Milano School of Medicine and San Raffaele Institute,

Milano, Italy

Residency

University of Milano School of Medicine and San Raffaele Institute, 2001

Milano, Italy

Certifications

  • Clinical Pharmacology

  • Pediatrics

Publications

Publications powered by Harvard Catalyst Profiles
  1. Sessa M, Lorioli L, Fumagalli F, Acquati S, Redaelli D, Baldoli C, Canale S, Lopez ID, Morena F, Calabria A, Fiori R, Silvani P, Rancoita PM, Gabaldo M, Benedicenti F, Antonioli G, Assanelli A, Cicalese MP, Del Carro U, Sora MG, Martino S, Quattrini A, Montini E, Di Serio C, Ciceri F, Roncarolo MG, Aiuti A, Naldini L, Biffi A. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet. 2016 Jul 30; 388(10043):476-87.
  2. Migliavacca M, Assanelli A, Ferrua F, Cicalese MP, Biffi A, Frittoli M, Silvani P, Chidini G, Calderini E, Mandelli A, Camporesi A, Milani R, Farinelli G, Nicoletti R, Ciceri F, Aiuti A, Bernardo ME. Pioglitazone as a novel therapeutic approach in chronic granulomatous disease. J Allergy Clin Immunol. 2016 Jun; 137(6):1913-1915.e2.
  3. Amit I, Baker D, Barker R, Berger B, Bertozzi C, Bhatia S, Biffi A, Demichelis F, Doudna J, Dowdy SF, Endy D, Helmstaedter M, Junca H, June C, Kamb S, Khvorova A, Kim DH, Kim JS, Krishnan Y, Lakadamyali M, Lappalainen T, Lewin S, Liao J, Loman N, Lundberg E, Lynd L, Martin C, Mellman I, Miyawaki A, Mummery C, Nelson K, Paz J, Peralta-Yahya P, Picotti P, Polyak K, Prather K, Qin J, Quake S, Regev A, Rogers JA, Shetty R, Sommer M, Stevens M, Stolovitzky G, Takahashi M, Tang F, Teichmann S, Torres-Padilla ME, Tripathi L, Vemula P, Verdine G, Vollmer F, Wang J, Ying JY, Zhang F, Zhang T. Voices of biotech. Nat Biotechnol. 2016 Mar; 34(3):270-5.
  4. Biffi A. Gene therapy for lysosomal storage disorders: a good start. Hum Mol Genet. 2016 Apr 15; 25(R1):R65-75.
  5. Cesani M, Lorioli L, Grossi S, Amico G, Fumagalli F, Spiga I, Filocamo M, Biffi A. Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy. Hum Mutat. 2016 Jan; 37(1):16-27.
  6. Ungari S, Montepeloso A, Morena F, Cocchiarella F, Recchia A, Martino S, Gentner B, Naldini L, Biffi A. Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy. Mol Ther Methods Clin Dev. 2015; 2:15038.
  7. Domi T, Porrello E, Velardo D, Capotondo A, Biffi A, Tonlorenzi R, Amadio S, Ambrosi A, Miyagoe-Suzuki Y, Takeda S, Ruegg MA, Previtali SC. Mesoangioblast delivery of miniagrin ameliorates murine model of merosin-deficient congenital muscular dystrophy type 1A. Skelet Muscle. 2015; 5:30.
  8. Biffi A. Clinical translation of TALENS: Treating SCID-X1 by gene editing in iPSCs. Cell Stem Cell. 2015 Apr 2; 16(4):348-9.
  9. Ricca A, Rufo N, Ungari S, Morena F, Martino S, Kulik W, Alberizzi V, Bolino A, Bianchi F, Del Carro U, Biffi A, Gritti A. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy. Hum Mol Genet. 2015 Jun 15; 24(12):3372-89.
  10. Cianciaruso C, Pagani A, Martelli C, Bacigaluppi M, Squadrito ML, Lo Dico A, De Palma M, Furlan R, Lucignani G, Falini A, Biffi A, Ottobrini L, Politi LS. Cellular magnetic resonance with iron oxide nanoparticles: long-term persistence of SPIO signal in the CNS after transplanted cell death. Nanomedicine (Lond). 2014 Jul; 9(10):1457-74.
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  12. Cesani M, Cavalca E, Macco R, Leoncini G, Terreni MR, Lorioli L, Furlan R, Comi G, Doglioni C, Zacchetti D, Sessa M, Scherzer CR, Biffi A. Metallothioneins as dynamic markers for brain disease in lysosomal disorders. Ann Neurol. 2014 Jan; 75(1):127-37.
  13. Lorioli L, Cesani M, Regis S, Morena F, Grossi S, Fumagalli F, Acquati S, Redaelli D, Pini A, Sessa M, Martino S, Filocamo M, Biffi A. Critical issues for the proper diagnosis of Metachromatic Leukodystrophy. Gene. 2014 Mar 10; 537(2):348-51.
  14. Morena F, di Girolamo I, Emiliani C, Gritti A, Biffi A, Martino S. A new analytical bench assay for the determination of arylsulfatase a activity toward galactosyl-3-sulfate ceramide: implication for metachromatic leukodystrophy diagnosis. Anal Chem. 2014 Jan 7; 86(1):473-81.
  15. Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013 Aug 23; 341(6148):1233151.
  16. Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, Naldini L. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013 Aug 23; 341(6148):1233158.
  17. Biffi A. Genetically-modified hematopoietic stem cells and their progeny for widespread and efficient protein delivery to diseased sites: the case of lysosomal storage disorders. Curr Gene Ther. 2012 Oct; 12(5):381-8.
  18. Capotondo A, Milazzo R, Politi LS, Quattrini A, Palini A, Plati T, Merella S, Nonis A, di Serio C, Montini E, Naldini L, Biffi A. Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation. Proc Natl Acad Sci U S A. 2012 Sep 11; 109(37):15018-23.
  19. Scaramuzza S, Biasco L, Ripamonti A, Castiello MC, Loperfido M, Draghici E, Hernandez RJ, Benedicenti F, Radrizzani M, Salomoni M, Ranzani M, Bartholomae CC, Vicenzi E, Finocchi A, Bredius R, Bosticardo M, Schmidt M, von Kalle C, Montini E, Biffi A, Roncarolo MG, Naldini L, Villa A, Aiuti A. Preclinical safety and efficacy of human CD34(+) cells transduced with lentiviral vector for the treatment of Wiskott-Aldrich syndrome. Mol Ther. 2013 Jan; 21(1):175-84.
  20. Visigalli I, Biffi A. Maintenance of a functional hematopoietic stem cell niche through galactocerebrosidase and other enzymes. Curr Opin Hematol. 2011 Jul; 18(4):214-9.
  21. Biffi A, Aubourg P, Cartier N. Gene therapy for leukodystrophies. Hum Mol Genet. 2011 Apr 15; 20(R1):R42-53.
  22. Biffi A, Bartolomae CC, Cesana D, Cartier N, Aubourg P, Ranzani M, Cesani M, Benedicenti F, Plati T, Rubagotti E, Merella S, Capotondo A, Sgualdino J, Zanetti G, von Kalle C, Schmidt M, Naldini L, Montini E. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection. Blood. 2011 May 19; 117(20):5332-9.
  23. Gentner B, Visigalli I, Hiramatsu H, Lechman E, Ungari S, Giustacchini A, Schira G, Amendola M, Quattrini A, Martino S, Orlacchio A, Dick JE, Biffi A, Naldini L. Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy. Sci Transl Med. 2010 Nov 17; 2(58):58ra84.
  24. Visigalli I, Delai S, Politi LS, Di Domenico C, Cerri F, Mrak E, D'Isa R, Ungaro D, Stok M, Sanvito F, Mariani E, Staszewsky L, Godi C, Russo I, Cecere F, Del Carro U, Rubinacci A, Brambilla R, Quattrini A, Di Natale P, Ponder K, Naldini L, Biffi A. Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model. Blood. 2010 Dec 9; 116(24):5130-9.
  25. Buono M, Visigalli I, Bergamasco R, Biffi A, Cosma MP. Sulfatase modifying factor 1-mediated fibroblast growth factor signaling primes hematopoietic multilineage development. J Exp Med. 2010 Aug 2; 207(8):1647-60.
  26. Visigalli I, Ungari S, Martino S, Park H, Cesani M, Gentner B, Sergi Sergi L, Orlacchio A, Naldini L, Biffi A. The galactocerebrosidase enzyme contributes to the maintenance of a functional hematopoietic stem cell niche. Blood. 2010 Sep 16; 116(11):1857-66.
  27. Fossati M, Cappelli B, Biral E, Chiesa R, Biffi A, Ossi C, Moro M, Cirillo DM, Clementi M, Soliman C, Ciceri F, Roncarolo MG, Fumagalli L, Marktel S. Fatal vancomycin- and linezolid-resistant Enterococcus faecium sepsis in a child undergoing allogeneic haematopoietic stem cell transplantation for beta-thalassaemia major. J Med Microbiol. 2010 Jul; 59(Pt 7):839-42.
  28. Noè A, Cappelli B, Biffi A, Chiesa R, Frugnoli I, Biral E, Finizio V, Baldoli C, Vezzulli P, Minicucci F, Fanelli G, Fiori R, Ciceri F, Roncarolo MG, Marktel S. High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome. Ital J Pediatr. 2010; 36:14.
  29. Chiesa R, Cappelli B, Crocchiolo R, Frugnoli I, Biral E, Noè A, Evangelio C, Fossati M, Roccia T, Biffi A, Finizio V, Aiuti A, Broglia M, Bartoli A, Ciceri F, Roncarolo MG, Marktel S. Unpredictability of intravenous busulfan pharmacokinetics in children undergoing hematopoietic stem cell transplantation for advanced beta thalassemia: limited toxicity with a dose-adjustment policy. Biol Blood Marrow Transplant. 2010 May; 16(5):622-8.
  30. Plati T, Visigalli I, Capotondo A, Buono M, Naldini L, Cosma MP, Biffi A. Development and maturation of invariant NKT cells in the presence of lysosomal engulfment. Eur J Immunol. 2009 Oct; 39(10):2748-54.
  31. Cesani M, Capotondo A, Plati T, Sergi LS, Fumagalli F, Roncarolo MG, Naldini L, Comi G, Sessa M, Biffi A. Characterization of new arylsulfatase A gene mutations reinforces genotype-phenotype correlation in metachromatic leukodystrophy. Hum Mutat. 2009 Oct; 30(10):E936-45.
  32. Cappelli B, Chiesa R, Evangelio C, Biffi A, Roccia T, Frugnoli I, Biral E, Noè A, Fossati M, Finizio V, Miniero R, Napolitano S, Ferrua F, Soliman C, Ciceri F, Roncarolo MG, Marktel S. Absence of VOD in paediatric thalassaemic HSCT recipients using defibrotide prophylaxis and intravenous Busulphan. Br J Haematol. 2009 Nov; 147(4):554-60.
  33. Bolis A, Coviello S, Visigalli I, Taveggia C, Bachi A, Chishti AH, Hanada T, Quattrini A, Previtali SC, Biffi A, Bolino A. Dlg1, Sec8, and Mtmr2 regulate membrane homeostasis in Schwann cell myelination. J Neurosci. 2009 Jul 8; 29(27):8858-70.
  34. Visigalli I, Moresco RM, Belloli S, Politi LS, Gritti A, Ungaro D, Matarrese M, Turolla E, Falini A, Scotti G, Naldini L, Fazio F, Biffi A. Monitoring disease evolution and treatment response in lysosomal disorders by the peripheral benzodiazepine receptor ligand PK11195. Neurobiol Dis. 2009 Apr; 34(1):51-62.
  35. Martino S, Tiribuzi R, Tortori A, Conti D, Visigalli I, Lattanzi A, Biffi A, Gritti A, Orlacchio A. Specific determination of beta-galactocerebrosidase activity via competitive inhibition of beta-galactosidase. Clin Chem. 2009 Mar; 55(3):541-8.
  36. Biffi A, Cesani M. Human hematopoietic stem cells in gene therapy: pre-clinical and clinical issues. Curr Gene Ther. 2008 Apr; 8(2):135-46.
  37. Biffi A, Naldini L. Novel candidate disease for gene therapy: metachromatic leukodystrophy. Expert Opin Biol Ther. 2007 Aug; 7(8):1193-205.
  38. Fraldi A, Biffi A, Lombardi A, Visigalli I, Pepe S, Settembre C, Nusco E, Auricchio A, Naldini L, Ballabio A, Cosma MP. SUMF1 enhances sulfatase activities in vivo in five sulfatase deficiencies. Biochem J. 2007 Apr 15; 403(2):305-12.
  39. Biffi A, Capotondo A, Fasano S, del Carro U, Marchesini S, Azuma H, Malaguti MC, Amadio S, Brambilla R, Grompe M, Bordignon C, Quattrini A, Naldini L. Gene therapy of metachromatic leukodystrophy reverses neurological damage and deficits in mice. J Clin Invest. 2006 Nov; 116(11):3070-82.
  40. Regis S, Lualdi S, Biffi A, Sessa M, Corsolini F, Parenti G, Filocamo M. Somatic intragenic recombination of the arylsulfatase A gene in a metachromatic leukodystrophy patient. Mol Genet Metab. 2006 Sep-Oct; 89(1-2):150-5.
  41. Biffi A, Naldini L. Gene therapy of storage disorders by retroviral and lentiviral vectors. Hum Gene Ther. 2005 Oct; 16(10):1133-42.
  42. Amendola M, Venneri MA, Biffi A, Vigna E, Naldini L. Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters. Nat Biotechnol. 2005 Jan; 23(1):108-16.
  43. Biffi A, De Palma M, Quattrini A, Del Carro U, Amadio S, Visigalli I, Sessa M, Fasano S, Brambilla R, Marchesini S, Bordignon C, Naldini L. Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells. J Clin Invest. 2004 Apr; 113(8):1118-29.
To schedule an appointment: Call 617-632-2204 or Request an Appointment

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