Arizona State University

Johns Hopkins University

Samira Kiani

Mo Reza Ebrahimkhani

Farzaneh Moghadam

Karen Anderson

Sri Krishna

Shayesteh Roshdi Ferdosi

Radwa Ewaisha

Xiao Wang

David Menn

Swechchha Pradhan

Jennifer Chapman

Jeremy Velazquez

Ryan LeGraw

Patrick Cahan

The present disclosure relates to synthetic liver organoids and methods of using such synthetic liver organoids for various applications including drug discovery and modeling human liver development. In particular, provided herein are methods of producing and using synthetic mature liver organoids comprising mature, functional cells found in the human liver.

Next generation designer liver organoids and their methods of preparation and use

Provided herein are methods and compositions for reducing an undesirable T cell immune response in human patients prior to and/or during gene therapy using CRISPR/Cas9-based genetic modulation.

Modulating human Cas9-specific host immune response

Aspects of the disclosure relate to methods and synthetic regulatory systems for more efficient nuclease-mediated homology-directed repair (HDR). In particular, provided herein are methods for more efficient in vivo and in vitro HDR-based gene editing where the methods comprise introducing into a cell a synthetic regulatory system comprising Cas nuclease, guide RNAs (gRNAs) having various lengths and configured to target distinct nucleotide sequences for simultaneous transcriptional repression (or activation) and genome editing via double stranded break and use of a donor nucleic acid molecule as a template for repair.

Universal platform to enhance CRISPR-based gene editing for in vivo therapies

Provided herein are CRISPR-based synthetic repression systems as well as methods and compositions using the synthetic repression systems to treat septicemia, an adverse immune response in a subject and Waldenström macroglobulinemia.

Synthetic immunomodulation with a CRISPR super-repressor in vivo

Aspects of the disclosure relate to synthetic regulatory systems composed of a multifunctional Cas nuclease, at least two guide RNAs (gRNAs) configured to target distinct nucleotide sequences, and a multilayered regulatory control element comprising ribozyme-based safety switches providing spatial and temporal control over the synthetic circuit in vivo.

CRISPR logic circuits for safer and controllable gene therapies

Provided herein are tools for understanding and engineering dynamics of synthetic genetic circuits which utilize CRISPR components. More particularly, methods, systems, and compositions for directing Cas9 activity using a fluorescent guide RNA (fgR-NA) which fluoresces in the presence of small molecules (e.g., DFHBI-IT) are described and illustrated in the present provisional application.

Growing community of inventors

Pittsburgh, PA, United States of America

Samira Kiani