A utilização da técnica CRISPR/Cas9 como um possível tratamento para a Distrofia Muscular de Duchenne (DMD): revisão de literatura
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Data
2023-12
Tipo de documento
Artigo Científico
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Área do conhecimento
Modalidade de acesso
Acesso fechado
Editora
Autores
SA, Nicolas Schorles Dourado
MOITINHO, Gabriel Di Clemente
MACEDO, Kleber Costa
Orientador
DASTOLI, Alessandra Finardi
Coorientador
Resumo
A Distrofia Muscular de Duchenne é uma doença grave e progressiva, causada por mutações, deleções e duplicações no gene DMD responsável pela produção de distrofina. A distrofina é uma proteína estrutural de 3685 aminoácidos que atua na ligação do citoesqueleto de actina com a matriz extracelular. É uma doença recessiva associada ao cromossomo X e afeta 1 a cada 3500-5000 meninos nascidos ao redor do mundo. Os principais sintomas são: atraso no desenvolvimento e dificuldade para se locomover, levando a quedas frequentes. Essa doença afeta o tecido muscular, esquelético e pode evoluir para morte prematura por complicações respiratórias e cardíacas. O diagnóstico é feito com base na avaliação física; histórico familiar; ressonância magnética; exames genéticos; exame de sangue e até mesmo biópsia. Essa doença não possui cura e o tratamento é paliativo, no qual, os corticosteroides são os mais utilizados para retardar a progressão da doença. Com o desenvolvimento da técnica de CRISPR/Cas9, diversos experimentos foram realizados no intuito de analisar a possibilidade da utilização dessa técnica para o tratamento definitivo da doença. As principais técnicas que estão sendo estudadas são: exon skipping; exon reframing; exon deletion; hdr correction; base editing (BEs); prime editing e terapia gênica. O presente artigo teve como objetivo realizar uma revisão da literatura a respeito do tratamento da DMD através da ferramenta CRISPR/Cas9. Em conclusão, a técnica de CRISPR possui um grande potencial no quesito de tratar a doença de forma definitiva, no entanto, ainda requer modificações para melhorar a entrega sistêmica e o funcionamento dessa ferramenta em humanos.
Duchenne Muscular Dystrophy is a serious and progressive disease caused by mutations, deletions or duplications in the DMD gene, responsible for the dystrophin production. Dystrophin is a structural protein of 3685 amino acids that acts in the connection of the actin cytoskeleton with the extracellular matrix. It is a recessive disease associated with the X chromosome and affects 1 in every 3500-5000 boys born around the world. The main symptoms are: developmental delay and difficulty to move around, leading to frequent falls. This disease affects muscle and skeletal tissue and can lead to premature death due to respiratory and cardiac complications. The diagnosis is made based on physical assessment; family history; magnetic resonance imaging; genetic tests; blood test and even biopsy. This disease has no cure and the treatment is palliative, in which corticosteroids are the most used to slow the progression of the disease. With the development of the CRISPR/Cas9 technique, several experiments were carried out. In order to analyze the possibility of using this technique for the definitive treatment of the disease. The main techniques being studied are: exon skipping; exon reframing; exon deletion; hdr correction; base editing (BEs); prime editing and gene therapy. The aim of this article was to carry out a literature review related to the treatment of DMD through the CRISPR/Cas9 tool. In conclusion, the CRISPR technique has great potential in terms of definitively treating the disease, however, it still requires modifications to improve the systemic delivery and functioning of this tool in humans.
Duchenne Muscular Dystrophy is a serious and progressive disease caused by mutations, deletions or duplications in the DMD gene, responsible for the dystrophin production. Dystrophin is a structural protein of 3685 amino acids that acts in the connection of the actin cytoskeleton with the extracellular matrix. It is a recessive disease associated with the X chromosome and affects 1 in every 3500-5000 boys born around the world. The main symptoms are: developmental delay and difficulty to move around, leading to frequent falls. This disease affects muscle and skeletal tissue and can lead to premature death due to respiratory and cardiac complications. The diagnosis is made based on physical assessment; family history; magnetic resonance imaging; genetic tests; blood test and even biopsy. This disease has no cure and the treatment is palliative, in which corticosteroids are the most used to slow the progression of the disease. With the development of the CRISPR/Cas9 technique, several experiments were carried out. In order to analyze the possibility of using this technique for the definitive treatment of the disease. The main techniques being studied are: exon skipping; exon reframing; exon deletion; hdr correction; base editing (BEs); prime editing and gene therapy. The aim of this article was to carry out a literature review related to the treatment of DMD through the CRISPR/Cas9 tool. In conclusion, the CRISPR technique has great potential in terms of definitively treating the disease, however, it still requires modifications to improve the systemic delivery and functioning of this tool in humans.
Palavras-chave
Distrofia Muscular de Duchenne (DMD), CRISPR/Cas9, Terapia Gênica, Tratamento