About

Stefano B Rivella, PhD, is a Professor of Pediatrics (Hematology) at the University of Pennsylvania's Perelman School of Medicine. He is the leader of the RNA Gene Therapeutics group at The Penn Institute for RNA Innovation. His research focuses on gene therapy approaches for blood disorders, including beta-thalassemia and other hematopoietic stem cell-related conditions. Dr. Rivella has contributed to the development of gene therapy techniques, including lentiviral genomic integrations, to cure blood diseases. His work involves exploring the molecular mechanisms of iron metabolism, erythropoiesis, and the genetic basis of blood disorders, aiming to improve therapeutic strategies for these conditions.

Research topics

• Medicine
• Biology
• Immunology
• Cell biology
• Internal medicine
• Genetics
• Cancer research
• Pathology
• Biochemistry

Selected publications

• In vivo hematopoietic stem cell modification by mRNA delivery

  Science · 2023 · 297 citations

  • Biology
  • Cell biology
  • Cancer research

  Hematopoietic stem cells (HSCs) are the source of all blood cells over an individual's lifetime. Diseased HSCs can be replaced with gene-engineered or healthy HSCs through HSC transplantation (HSCT). However, current protocols carry major side effects and have limited access. We developed CD117/LNP-messenger RNA (mRNA), a lipid nanoparticle (LNP) that encapsulates mRNA and is targeted to the stem cell factor receptor (CD117) on HSCs. Delivery of the anti-human CD117/LNP-based editing system yielded near-complete correction of hematopoietic sickle cells. Furthermore, in vivo delivery of pro-apoptotic PUMA (p53 up-regulated modulator of apoptosis) mRNA with CD117/LNP affected HSC function and permitted nongenotoxic conditioning for HSCT. The ability to target HSCs in vivo offers a nongenotoxic conditioning regimen for HSCT, and this platform could be the basis of in vivo genome editing to cure genetic disorders, which would abrogate the need for HSCT.

  PublisherOA PDFDOI

• Tmprss6-ASO as a tool for the treatment of Polycythemia Vera mice

  PLoS ONE · 2021 · 21 citations

  Senior authorCorresponding
  • Medicine
  • Cancer research
  • Internal medicine

  Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm resulting from an acquired driver mutation in the JAK2 gene of hematopoietic stem and progenitor cells resulting in the overproduction of mature erythrocytes and abnormally high hematocrit, in turn leading to thromboembolic complications. Therapeutic phlebotomy is the most common treatment to reduce the hematocrit levels and consequently decrease thromboembolic risk. Here we demonstrate that, by using the iron restrictive properties of the antisense oligonucleotides against Tmprss6 mRNA, we can increase hepcidin to achieve effects equivalent to therapeutic phlebotomy. We provide evidence that this less invasive approach could represent an additional therapeutic tool for the treatment of PV patients.

  PublisherOA PDFDOI

• DNA binding to TLR9 expressed by red blood cells promotes innate immune activation and anemia

  Science Translational Medicine · 2021 · 201 citations

  • Biology
  • Immunology
  • Cell biology

  Red blood cells detect and bind cell-free nucleic acids, contributing to anemia and immune cell activation during acute inflammation.

  PublisherOA PDFDOI

Recent grants

• Regulatory Role of Transferrin in Erythropoiesis and Iron Metabolism

  NIH · $5.4M · 2012–2027

• NIH Grant R21DK065169

  NIH · $326k · 2007

• Activin signaling in normal and disordered erythropoiesis

  NIH · $5.2M · 2010–2023

• NIH Grant R21DK071575

  NIH · $457k · 2009

• NIH Grant K01DK063992

  NIH · $667k · 2010

Frequent coauthors

• Laura Breda

  University of Chieti-Pescara

  152 shared

• Carla Casu

  Children's Hospital of Philadelphia

  98 shared

• Sara Gardenghi

  Children's Hospital of Philadelphia

  77 shared

• Patricia J. Giardina

  57 shared

• Amaliris Guerra

  Children's Hospital of Philadelphia

  54 shared

• Robert W. Grady

  Cornell University

  50 shared

• Pedro Luiz Ramos

  47 shared

• Yelena Ginzburg

  Icahn School of Medicine at Mount Sinai

  47 shared

Labs

• Rivella LabPI

Education

• Postdoctoral Scientist, Human Genetics

  Memorial Sloan-Kettering Cancer Center

  2002

• Research Fellow, Genetics

  University of Pavia

  1997

• B.Sc., Genetics

  University of Pavia

  1990

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• John Q. Trojanowskih-296
• Craig B. Thompsonh-277
• Daniel J Raderh-236
• Carl H. Juneh-218
• M. Celeste Simonh-185