Methods and pharmaceutical compositions for expressing a polynucleotide of interest in the peripheral nervous system of a subject

Patent metadata

Field	Value
Publication number	US-10801040-B2
Application number	US-201615740036-A
Country	US
Kind code	B2
Filing date	Jul 6, 2016
Priority date	Jul 7, 2015
Publication date	Oct 13, 2020
Grant date	Oct 13, 2020

Abstract

The present invention relates to methods and pharmaceutical compositions for expressing a polynucleotide of interest in the peripheral nervous system of a subject. In particular, the present invention relates to a method for selectively expressing a polynucleotide of interest in the peripheral nervous system of a subject in need thereof comprising the step of transducing a peripheral nerve of the subject with an amount of an AVV9 vector containing the polynucleotide of interest.

First claim

The invention claimed is:

1. A method for expressing a polynucleotide in myelinating Schwann cells of a subject with a peripheral demyelinating disease, comprising
injecting an AAV9 vector that encodes the polynucleotide into a peripheral nerve of the subject, wherein the AAV9 vector preferentially transduces the myelinating Schwann cells over non-myelinating Schwann cells along the peripheral nerve, and wherein the polynucleotide is expressed in transduced myelinating Schwann cells along the peripheral nerve.

2. The method of claim 1 , wherein the peripheral demyelinating disease is selected from the group consisting of hereditary peripheral demyelinating diseases and acquired peripheral demyelinating diseases.

3. The method of claim 1 , wherein the peripheral demyelinating disease is selected from the group consisting of Refsum's disease, Abetalipoproteinemia, Tangier disease, Krabbe's disease, Metachromatic leukodystrophy, Fabry's disease, Dejerine-Sottas syndrome, and Charcot-Marie-Tooth Diseases.

4. The method of claim 1 , wherein the peripheral demyelinating disease is selected from the group consisting of diabetic neuropathies, immune-mediated neuropathies, acute motor neuropathy, acute sensory neuropathy, acute autonomic neuropathy, chronic polyneuropathies, peripheral demyelinating diseases associated with vasculitis or inflammation of the blood vessels in peripheral nerves, peripheral demyelinating diseases associated with monoclonal gammopathies, peripheral demyelinating diseases associated with tumors or neoplasms, peripheral demyelinating diseases caused by infections, peripheral demyelinating diseases caused by nutritional imbalance, peripheral demyelinating diseases arising in kidney diseases, hypothyroid neuropathies, peripheral demyelinating diseases caused by alcohol and toxins, peripheral demyelinating diseases caused by trauma or compression, and idiopathic peripheral demyelinating diseases.

5. The method of claim 1 , wherein the polynucleotide is an antisense oligonucleotide construct.

6. The method of claim 1 , wherein the polynucleotide is a siRNA.

7. The method of claim 1 , wherein the polynucleotide is operatively linked to a promoter sequence.

8. The method of claim 1 , wherein the AAV9 vector does not transduce axons.

9. The method of claim 1 , wherein about 97% of the myelinating Schwann cells are transduced.

10. The method of claim 1 , wherein the subject is a primate.

Assignees

• Inst Nat Sante Rech Med
• Univ Paris Sud
• Commissariat Energie Atomique
• Assist Publique Hopitaux Paris Aphp
• Univ Montpellier

Inventors

• Aubourg Patrick
• Tricaud Nicolas
• Gautier Benoît

Classifications

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• C12N2750/14143

  viral genome or elements thereof as genetic vector · CPC title

• C12N2310/11

  Antisense · CPC title

• A61K35/761

  Adenovirus · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title