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Nano-genE: NANO-TRANSDUCERS FOR GENE EDITING

​ CRISPR/Cas9​ Gene therapy​ NanotransducerEditing geneticoGenetic editingTechShareDay-d1w3

Introduction

The invention describes a nano-transducer able to modify a target genomic sequence in a cell, in order to eliminate harmful mutations underlying genetic diseases. The new Nano-gen genomic editing tool overcomes the limitations of CRISPR/Cas9 systems by replacing the nuclease activity of Cas9 with a nano-transducer. The nano-transducer activation is bound by the occurrence of a series of conditions, giving the system greater reliability and specificity.

Technical features

The main innovative aspect of Nano-genE is that the nano-transducer consists of a hybrid system, which includes: 1) a nanoparticle covalently bound to a g-RNA/dCas9 (a mutated Cas9 able to bind DNA to the target site via g-RNA but unable to cut DNA) and 2) a restriction enzyme that only activates at 65 °C. The nanoparticle is designed to absorb energy at a specific wavelength and convert it into heat. Activation of the nano-transducer, as a result of  laser irradiation, causes localized temperature increase, only in the gene locus recognized by ribonucleoprotein. At 65 °C the activated restriction enzyme causes the double-stranded DNA to be cut into the chosen gene locus. The superiority of Nano-Gene technology over current methodologies lies in multi-function integration: time (editing occurs only when the laser is on), space (editing occurs only where the laser is focused) and the fidelity function (editing only takes place if the nano-transducer is on-target).

Possible Applications

  • Medicine;
  • Gene therapy;
  • Treatment of pathologies triggered by specific DNA aberrations:​ Cancer, Rare diseases.

Advantages

  • High specificity on the target gene;
  • Minimization of side effects, as non-specific genome cutting;
  • Independence from the activity of Cas9;
  • Limited activity of Cas9 on genome exposure;
  • Reduced toxicity compared to CRISPR/Cas9; 
  • Compatibility with a multi-gene treatment.