MENU
X
Close Menu CLOSE

A Single Administration of CRISPR/Cas9 Lipid Nanoparticles Achieves Robust and Persistent In Vivo Genome Editing


Authors: J. Finn, A. Smith, M. Patel, L. Shaw, M. Youniss, J. Heteren, T. Dirstine, C. Ciullo, R. Lescarbeau, J. Seitzer, R. Shah, A. Shah, D. Ling, J. Growe, M. Pink, E. Rohde, K. Wood, W. Salomon, W. Harrington, C. Dombrowski, W. Strapps, Y. Chang, D. Morrissey

Journal: Cell Reports

DOI: 10.1016/j.celrep.2018.02.014

Publication - Abstract

February 27, 2018

Abstract:

The development of clinically viable delivery methods presents one of the greatest challenges in the therapeutic application of CRISPR/Cas9 mediated genome editing. Here, we report the development of a lipid nanoparticle (LNP)-mediated delivery system that, with a single administration, enabled significant editing of the mouse transthyretin (Ttr) gene in the liver, with a >97% reduction in serum protein levels that persisted for at least 12 months. These results were achieved with an LNP delivery system that was biodegradable and well tolerated. The LNP delivery system was combined with a sgRNA having a chemical modification pattern that was important for high levels of in vivo activity. The formulation was similarly effective in a rat model. Our work demonstrates that this LNP system can deliver CRISPR/Cas9 components to achieve clinically relevant levels of in vivo genome editing with a concomitant reduction of TTR serum protein, highlighting the potential of this system as an effective genome editing platform.

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Blog Posts
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Summary

Systemic Messenger RNA Therapy as a Treatment for Methylmalonic Acidemia

An D, Schneller JL, Frassetto A, Liang S, Zhu X, Park JS, Theisen M, Hong SJ,Zhou J, Rajendran R, BeccaLevy B, Howell R, Besin G, Presnyak V, Sabnis S, Murphy-Benenato KE , Kumarasinghe ES,Salerno T, Martini PGV

Inborn errors of metabolism (IEMs) can be relatively straight forward to screen for and diagnose; these disorders however, have currently very limited options for treatment. Methylmalonic acidemia (MMA), is an IEM caused by complete or partial defi...

Read More


Publication - Abstract

Mast cells are important immune cells that have significant roles in mediating allergy and asthma. Therefore, studying the molecular mechanisms regulating these and other processes in mast cells is important to elucidate. Methods such as lipofectio...

Read More


Get Started

To learn how Precision NanoSystems accelerates nanomedicine development from an idea to clinical applications, contact our Technical Sales Team.

Get in Touch

Stay Informed

Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.