Genetic conversion of an SMN2 gene to SMN1: A novel approach to the treatment of spinal muscular atrophy

DiMatteo, Darlise; Callahan, Stephanie; Kmiec, Eric B.

doi:10.1016/j.yexcr.2007.10.012

Cited by 31 publications

(16 citation statements)

References 34 publications

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“…We found the latter explanation more convincing based on our observation in normal individuals. Of note, a recent in vitro study highlights the significance of our SMN2-to-SMN1 conversion finding by showing that it can even be driven by using single-stranded oligonucleotides [23]. Given that SMN1 genes can produce more stable and biologically active SMN protein, creating an SMN1-like gene converted from SMN2 in SMA patients might be an appealing target for gene therapy [24].…”

Section: Discussionmentioning

confidence: 90%

Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Chen

Tzeng

Wang

et al. 2011

Journal of the Neurological Sciences

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Section: Discussionmentioning

confidence: 90%

Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Chen

Tzeng

Wang

et al. 2011

Journal of the Neurological Sciences

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“…While the exact mechanism of oligonucleotide-mediated gene editing is still under investigation, more recent advances have focused on chemically modifi ed ssODNs that have been shown to increase the effi ciency of this approach [ 50 , 112 ]. ssODNs have been shown to introduce targeted genetic corrections in transfected cells to address disease-related mutations for SMA [ 113 ] and DMD [ 114 ].…”

Section: Genetic Modifi Cation With Oligonucleotide Complexesmentioning

confidence: 99%

Genome Editing for Neuromuscular Diseases

Ousterout

Gersbach

2016

Advances in Experimental Medicine and Biology

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Neuromuscular diseases are a diverse range of conditions that include myopathic and neuropathic disorders related to muscular dysfunction. Inherited neuromuscular diseases are the result of a broad spectrum of genetic mutations, including point mutations, insertions and deletions, chromosomal rearrangements, epigenetic aberrations, and repeat expansions or contractions. Targeted genome editing is a promising method to correct the inherited mutations underlying these disorders. Over the last decade there have been many signifi cant advances in engineering targeted DNA-binding proteins to manipulate specifi c sequences of complex genomes. These genome editing tools are rapidly becoming viable therapeutics that will allow the targeted addition, exchange, or removal of almost any genetic sequence in the human genome. In this chapter, selected neuromuscular diseases representing inherited myopathies or neuropathies are discussed. The genome editing tools available to create targeted genetic modifi cations are reviewed. Promising cell-and gene-based therapies are introduced in the context of the treatment of neuromuscular disorders in combination with genome editing therapies. Finally, specifi c examples of how genome editing may be applied to correct the genetic basis of particular neuromuscular disorders are presented and discussed.

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“…Finally, substances with a neuroprotective action, (such as cardiotrophin-1), 50 and genetic conversion of the SMN 2 gene into SMN 1 , 51 are also the subject of therapeutic proposals being studied.…”

Section: Future Prospects For Diagnosis and Treatment Of Smamentioning

confidence: 99%

Atrofia muscular espinhal: diagnóstico, tratamento e perspectivas futuras

Baioni¹,

Ambiel²

2010

J. Pediatr. (Rio J.)

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Objective: To report on recent genetic and molecular discoveries and on future prospects for the treatment of spinal muscular atrophy (SMA), thereby helping healthcare professionals to make a quick diagnosis and provide appropriate and timely therapeutic support.Sources: Information was collected from scientific articles published in the last 2 decades, retrieved from the databases SciELO, PubMed, and MEDLINE. Summary of the findings:SMA is a neurodegenerative disorder with autosomal recessive genetic heredity. It is caused by a homozygous deletion of the survival motor neuron (SMN 1 ) gene. This genetic alteration results in reduced levels of the SMN protein, leading to degeneration of alpha motor neurons of the spinal cord and resulting in muscle weakness and progressive symmetrical proximal paralysis. It is known that basic nutritional and respiratory care and physiotherapy can be important to delaying disease progression and prolonging patients' lives. Several drugs are being tested, some new, others, such as valproic acid, already known; paralysis can be halted, but not reversed. Conclusions:SMA is a difficult to diagnose disorder, because it is little known, and treatment is uncertain. Pharmacological treatments and supportive therapies are not yet able to recover motor neurons or muscle cells that have already been lost, but are aimed at delaying disease progression and improving patients' residual muscle function, as well as offering better quality of life and life expectancy.

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Genetic conversion of an SMN2 gene to SMN1: A novel approach to the treatment of spinal muscular atrophy

Cited by 31 publications

References 34 publications

Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Identification of bidirectional gene conversion between SMN1 and SMN2 by simultaneous analysis of SMN dosage and hybrid genes in a Chinese population

Genome Editing for Neuromuscular Diseases

Atrofia muscular espinhal: diagnóstico, tratamento e perspectivas futuras

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