APLICAÇÕES DE CRISPR-CAS9 NA CORREÇÃO DA MUTAÇÃO DA TALASSEMIA BETA: AVANÇOS TECNOLÓGICOS, DESAFIOS TRANSLACIONAIS E PERSPECTIVAS FUTURAS
DOI:
https://doi.org/10.61164/ef6z6361Palavras-chave:
Gene HBB; Hemoglobina Fetal; Edição Gênica; BCL11A.Resumo
A β-talassemia é uma hemoglobinopatia hereditária causada por mutações no gene HBB, que comprometem a síntese da cadeia β da hemoglobina, resultando em anemia crônica e dependência transfusional. A terapia gênica baseada em CRISPR-Cas9 surge como uma alternativa promissora para corrigir essas mutações, permitindo tanto a restauração direta da expressão da β-globina quanto a reativação terapêutica da hemoglobina fetal (HbF) por meio da modulação de elementos regulatórios como o BCL11A. Esta revisão bibliográfica, de caráter narrativo e analítico, examina os principais avanços tecnológicos e clínicos relacionados ao uso do sistema CRISPR-Cas9 e suas variantes (Cas12a, base editing e prime editing) na β-talassemia, com ênfase em segurança genômica, eficiência terapêutica e viabilidade de implementação. São abordados métodos de entrega como RNP, AAV6 e nanopartículas lipídicas, além de estratégias de edição in vivo e integração de inteligência artificial no design de gRNAs. Apesar dos progressos, desafios persistem quanto aos efeitos off-target, ativação de p53, estabilidade clonal e custos elevados que limitam a aplicabilidade em sistemas públicos de saúde, especialmente no contexto brasileiro. Conclui-se que, embora ainda em fase translacional, o CRISPR-Cas9 representa uma das ferramentas mais revolucionárias para o tratamento curativo da β-talassemia, abrindo caminho para terapias mais seguras, precisas e acessíveis, nas quais o biomédico desempenha papel essencial na validação técnica, monitoramento e biossegurança laboratorial.
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POLÍTICA DE PRIVACIDADE
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Obs: todo o conteúdo do trabalho é de responsabilidade do autor e orientador.
