68 results about "Dystrophin gene" patented technology

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

The invention relates to meganuclease variants which cleave a DNA target sequence from the human dystrophin gene (DMD), to vectors encoding such variants, to a cell, an animal or a plant modified by such vectors and to the use of these meganuclease variants and products derived therefrom for genome therapy, ex vivo (gene cell therapy) and genome engineering including therapeutic applications and cell line engineering. The invention also relates to the use of meganuclease variants for inserting therapeutic transgenes other than DMD at the dystrophin gene locus, using this locus as a safe harbor locus. The invention also relates to the use of meganuclease variants for using the dystrophin gene locus as a landing pad to insert and express genes of interest.

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

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 stem-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.

The present invention provides a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene.

The present invention provides a pharmaceutical agent which causes skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene with a high efficiency.The present invention provides an oligomer which efficiently enables to cause skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene.

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 59.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Provided is a drug that allows highly-efficient skipping of exon 51 in the human dystrophin gene. The present invention provides an antisense oligomer which enables exon 51 in the human dystrophin gene to be skipped.

The present invention provides a pharmaceutical agent which causes skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene with a high efficiency. The present invention provides an oligomer which efficiently enables to cause skipping of the 55th, 45th, 50th or 44th exon in the human dystrophin gene.

Duchenne muscular dystrophy (DMD) is a progressive muscle disease that is caused by severe defects in the dystrophin gene and results in the patient's death by the third decade. The present invention utilizes the Double Mutant mice (DM) as an appropriate human model for DMD as these mice are deficient for both dystrophin and utrophin (mdx / +, utrn − / −), die at 3 months of age and suffer from severe muscle weakness, pronounced growth retardation, kyphosis, weight loss, slack posture, and immobility. Expression from a transgene of novel human retinal dystrophin Dp260 was shown to prevent premature death and reduce the severe muscular dystrophy phenotype to a mild clinical myopathy. Electromyography, histology, radiography, magnetic resonance imaging, and behavior studies concluded that DM transgenic mice grew normally, had normal spinal curvature and mobility, and had reduced muscle pathology. EMG and histologic data from transgenic DM mice showed decreased abnormalities to levels typical of mild myopathy, while the DM mice exhibited severe abnormalities commonly seen in human dystrophinopathies. The transgenic DM mice also had measurable movement levels comparable to those of untreated mdx mice and controls.

Methods of modifying a dystrophin gene are disclosed, for restoring dystrophin expression within a cell having an endogenous frameshift mutation within the dystrophin gene. The methods comprising introducing a first cut within an exon of the dystrophin gene creating a first exon end, wherein said first cut is located upstream of the endogenous frameshift mutation; and introducing a second cut within an exon of the dystrophin gene creating a second exon end, wherein said second cut is located downstream of the frameshift mutation. Upon joining / ligation of said first and second exon ends dystrophin expression is restored, as the correct reading frame is restored. Reagents and uses of the method are also disclosed, for example to treat a subject suffering from muscular dystrophy.

Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Disclosed herein are vectors that targets a dystrophin gene, encoding at least one Cas9 molecule or a Cas9 fusion protein, and at least one gRNA molecule (e.g., two gRNA molecules), and compositions and cells comprising such vectors. Also provided are methods for using the vectors, compositions and cells for genome engineering (e.g., correcting a mutant dystrophin gene), and for treating DMD.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

Provided is a drug that allows highly-efficient skipping of exon 51 in the human dystrophin gene. The present invention provides an antisense oligomer which enables exon 51 in the human dystrophin gene to be skipped.

This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 45 skipping are described.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

CRISPR / Cas9-mediated genome editing holds clinical potential for treating genetic diseases, such as Duchenne muscular dystrophy (DMD), which is caused by mutations in the dystrophin gene. Here, usingthree promoters to drive expression of the same DMD guide RNA, a more robust and safe form of genome editing was achieved in a humanized mouse model for DMD with a deletion in exon 50, and in a DeltaEx50-MD Dog.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.