San Raffaele Telethon Institute for Gene Therapy

Epigenetic regulation and targeted genome editing


Group Leader

Angelo Lombardo


This Group is interested in developing innovative approaches to treat diseases and to study fundamental biological questions. To this end, we recently developed a novel strategy to permanently silence gene expression through targeted epigenetic editing. We are exploiting this innovate strategy to: (i) tackle inherited diseases for which gene silencing is a valid therapeutic solution, such as hemoglobinopathies and familial hypercholesterolemia; (ii) determine the specificity and persistence of epigenetic silencing across cell development and differentiation, two key aspects for effective and safe exploitation of the technology; (iii) shed light into the fundamental principles governing establishment and maintenance of epigenetic silencing, basic biological information that can potentially be used to further improve the platform.

Research activity

To accomplish these goals, we are taking advantage of stealth and effective gene delivery procedures, relevant disease models, genome-scale loss-of-function and single-cell transcriptomic analyses, in collaborations with internationally renowned scientists. Finally, building on our extensive experience in targeted genome editing, we are now expanding our field of research to include cell and organ transplantation. To this end, we are:

  1. coupling state-of-the-art gene editing and cell reprogramming procedures to generate off-the-shelf immunocompatible allogeneic cells for tissue transplantation;
  2. harnessing the differentiation potential of pluripotent stem cells to derive interspecies chimera with potential clinical applications.