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Nanoblades: shuttles for genome surgery



Researchers are now able to edit the genome with precision using the “gene editing scissors” of CRISPR-Cas9, which is a highly promising tool for gene therapy. The technical challenge now is to get this tool into the genome of certain cells. With this in mind, a joint team from Inserm, the CNRS, the Université Claude Bernard Lyon 1, and the École Normale Supérieure de Lyon, working within the International Center for Infectiology Research (CIRI), have developed capsules that allow CRISPR-Cas9 to reach the target DNA: Nanoblades. Described in a recent article in Nature Communications, they open up avenues of research for genome editing in human stem cells.

Since 2012, the scientific community has had access to a revolutionary method for highly precise genome “surgery”: the CRISPR-Cas9 system. These molecular scissors are able to cut DNA at a precise place in a wide variety of cell types. The technique therefore offers significant prospects for research and human health. However, getting these “gene editing scissors” to their target—including the genome of certain stem cells—remains technically challenging.

Tackling this problem has been the focus for research teams from Inserm, the CNRS, the Université Claude Bernard Lyon 1, and the École Normale Supérieure de Lyon, who have developed Nanoblades,[1] particles that enable CRISPR-Cas9 to be delivered into numerous different cells, including human cells.

The scientists had the idea of encapsulating the CRISPR-Cas9 system in structures that strongly resemble viruses as a way to deliver it into target cells, by fusing with the target cell membrane.

In developing Nanoblades, researchers exploited the properties of the retroviral Gag protein, which is able to produce viral particles that have no genome and are therefore non-infectious. The research team fused the Gag protein from a mouse retrovirus with the Cas9 protein—the scissor component of the CRISPR system. This new “fusion” protein is what makes Nanoblades original.

As a result, and unlike classic genome modification techniques, Nanoblades encapsulate a CRISPR/Cas9 complex that is immediately functional rather than delivering a nucleic acid coding for the CRISPR-Cas9 system in the treated cells. “The action of CRISPR-Cas9 on the cells is therefore temporary. It is also more precise and preserves the non-target regions of the genome, which is a particularly important feature in the context of therapeutic applications”, explain the authors.


Représentation schématique d’une particule Nanoblades livrant CRISPR CAS9

Schematic diagram of a Nanoblades particle delivering CRISPR-Cas9

La protéine GAG tapissant l’intérieur des particules rétrovirales

The Gag protein internally lining the retroviral particles

La protéine CAS9, ciseau effecteur du système CRISPR, pouvant cliver l’ADN

The Cas9 protein, the scissor component of the CRISPR system, is able to cleave DNA

L’ARN guide, qui va placer CAS9 sur la région ADN cible. Il a une affinité naturelle pour CAS9

The RNA guides Cas9, then positions it at the target DNA region. It has a natural affinity for Cas9

Les deux enveloppes virales conférant un tropisme large aux particules

The two viral envelopes give the particles a broad tropism

La bicouche lipidique qui entoure la particule

The lipid bilayer surrounding the particle

Finally, researchers used an original combination of two viral envelope proteins on the surface of Nanoblades to enable them to enter a wide range of target cells.

The scientists have demonstrated the efficacy of Nanoblades in vivo, in mouse embryos, for a broad range of applications and in a broad panel of target cells for which other methods have had limited success. “Nanoblades have turned out to be particularly effective for editing the genome of human stem cells. These cells are of major therapeutic interest (particularly in tissue regeneration), but remain difficult to manipulate using standard methods”, explain the study authors.

[1] Nanoblades have been tested in mice and were patented by Inserm Transfert in 2016.

Researcher Contact

Emiliano Ricci

Chercheur Inserm

Unité 1111 / UMR5308 Centre international de recherche en infectiologie (CIRI)

Equipe « Contrôle traductionnel des ARN eucaryotes et viraux »

T +33 (0)4 72 72 89 53



Philippe Mangeot

Chercheur Inserm

Unité 1111 / UMR5308 Centre international de recherche en infectiologie (CIRI)

Equipe « Contrôle traductionnel des ARN eucaryotes et viraux »

T +33 (0)4 72 72 80 51


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Genome editing in primary cells and in vivo using viral-derived “Nanoblades” loaded with Cas9/sgRNA ribonucleoproteins


Philippe E. Mangeot1*, Valérie Risson2§, Floriane Fusil1§, Aline Marnef3§, Emilie Laurent1, Juliana Blin1, Virginie Mournetas4, Emmanuelle Massouridès4, Thibault J. M. Sohier1, Antoine Corbin1, Fabien Aubé5, Marie Teixeira6, Christian Pinset4, Laurent Schaeffer2, Gaëlle Legube3, François-Loïc Cosset1, Els Verhoeyen1, Théophile Ohlmann1, Emiliano P. Ricci1,5*.


1 CIRI – International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, F-69007, Lyon, France.

2 Institut NeuroMyoGène, CNRS 5310, INSERM U121, Université Lyon1, Faculté de Médecine Lyon Est, Lyon, France.

3 LBCMCP, Centre de Biologie Intégrative (CBI), CNRS, Université de Toulouse, UT3, 118 Route de Narbonne, 31062 Toulouse, France.

4 I-STEM/CECS, Inserm UMR861 28 rue Henri Desbruères, 91100 Corbeil Essonnes,France.

5 Laboratory of Biology and Modelling of the Cell, UnivLyon, ENS de Lyon, Univ Claude Bernard, CNRS UMR 5239, INSERM U1210, Laboratoire de Biologie et Modélisation de la Cellule, Lyon, France.

6 SFR BioSciences, Plateau de Biologie Expérimentale de la Souris (AniRA-PBES), Ecole Normale Supérieure de Lyon, Université Lyon1, CNRS UMS3444, INSERM US8, 69007, Lyon, France.

  • Equal contribution


Nature Communications :