Institut National De La Sante Et De La Recherche Medicale

Association Institut De Myologie

Centre National De La Recherche Scientifique

Université Pierre Et Marie Curie (Paris 6)

Synthena Ag

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Sorbonne Université

Universitât Bern

Genethon

Université De La Méditerranée - Aix-Marseille Ii

Universitat Ber

Université Pierre Et Marie Curie

Luis Garcia

Thomas Voit

Aurelie Avril

Christian Leumann

Denis Furling

Cyriaque Beley

Robert Michael Kotin

Nicolas Levy

Fedor Svinartchouk

Lina Li

Stéphanie Lorain

Daniel Schumperli

Jérôme Denard

Martin Krahn

Marc Bartoli

Daniel Schümperli

Aurélie Avril

The invention relates to nucleic acids and methods for restoring acid alpha-glucosidase (GAA) activity in patients with Pompe disease using splice-switching technology.

Nucleic acids and methods for the treatment of Pompe disease

Provided are tricyclo-DNA (tc-DNA) AON and methods employing tc-DNA AON for modifying splicing events that occur during pre-mRNA processing. Tricyclo-DNA (tc-DNA) AON are described that may be used to facilitate exon skipping or to mask intronic silencer sequences and/or terminal stein-loop sequences during pre-mRNA processing and to target RNase-mediated destruction of processed mRNA. Tc-DNA AON described herein may be used in methods for the treatment of Duchenne Muscular Dystrophy by skipping a mutated exon 23 or exon 51 within a dystrophin gene to restore functionality of a dystrophin protein; in methods for the treatment of Spinal Muscular Atrophy by masking an intronic silencing sequence and/or a terminal stem-loop sequence within an SMN2 gene to yield modified functional SMN2 protein, including an amino acid sequence encoded by exon 7, which is capable of at least partially complementing a non-functional SMN1 protein; and in methods for the treatment of Steinert's Myotonic Dystrophy by targeting the destruction of a mutated DM1 mRNA comprising 3'-terminal CUG repeats.

Tricyclo-DNA antisense oligonucleotides, compositions, and methods for the treatment of disease

The present invention relates to a nucleic acid molecule containing a sequence of tricyclo nucleosides joined by internucleoside phosphorothioate linkage. The invention also relates to synthetic antisense oligonucleotides and to methods employing the same.

Tricyclo-phosphorothioate DNA

An isolated linear nucleic acid molecule comprising in this order: a first adeno-associated virus (AAV) inverted terminal repeat (ITR), a nucleotide sequence of interest and a second AAV ITR, wherein said nucleic acid molecule is devoid of AAV capsid protein coding sequences. The said nucleic acid molecule can be applied to a host at repetition without eliciting an immune response. Methods for producing and purifying this nucleic acid molecule, and use of the same for therapeutic purposes are also provided.

Capsid-free AAV vectors, compositions, and methods for vector production and gene delivery

Methods for increasing the efficiency of target tissue penetration of an adeno-associated virus (AAV) vector in a patient are provided. In some aspects, the methods involve inhibiting the interaction of the serum protein galectin 3 binding protein (G3BP) with AAV vector. Further provided are methods for reducing tissue distribution of a virus or for neutralizing a virus harbored by an organ destined for transplant, or newly transplanted, by administering a composition comprising G3BP.

Methods of increasing efficiency of vector penetration of target tissue

The present invention provided methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated simple or double trans-splicing. The compositions of the invention include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and to mediate a simple or double trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (Chimeric RNA).

Nucleic acid molecules and methods for exchanging exon(s) by transsplicing

The present invention relates to a method to improve the activity of engineered U7 snRNAs used in the context of RNA-based therapeutics; particularly in exon skipping, exon inclusion, and mRNA eradication strategies. The resulting modified U7 snRNAs are useful for treating neuromuscular diseases, in particular Duchenne neuromuscular dystrophy, myotonic dystrophy DM1 and spinal muscular atrophy.

Modified U7 snRNAs for treatment of neuromuscular diseases

The present invention relates to methods for restoring the function of a mutated dysferlin comprising the step of preventing splicing of one or more exons which encode amino acid sequences that cause said dysferlin dysfunction. Particularly, the splicing of exon 32 is prevented. The present invention also relates to a method for treating a dysferlinopathy in a patient in need thereof, comprising the step of administering to said patient antisense oligonucleotides complementary to nucleic acid sequences that are necessary for correct splicing of one or more exons which encode amino acid sequences that cause said dysfunction. Particularly, the splicing of exon 32 is prevented.

Exon skipping therapy for dysferlinopathies

Growing community of inventors

Bailly, France

Luis Garcia