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Correction of sickle-cell anemia using CRISPR-Cas9 system in hematopoietic stem cells

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Resumo:Drepranocitosis (or sickle cell anemia - SCA) is a genetic hereditary disease that affects millions of people worldwide, bearing significant clinical features and a compromised prognosis with increased recurrences of crisis. Many treatments have been suggested to help dealing with sickle cell anemia, either by reducing and managing the consequences of the disease, or even by trying to solve it (bone marrow transplant). However, until date, there has not been developed a “perfect” therapeutic approach. Gene therapy has been used as the ultimate weapon to treat diseases whose cure cannot be achieved with traditional methods. CRISPR-Cas9 showed to be potentially safer and more efficient in treating SCD than other conventional gene therapies, which is presumed to be a result of the precision of the correction of this tool and the lack of use of viral vectors. Comparing with other available gene-editing techniques, namely zinc finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs), CRISPR/Cas9 offers some advantages, as well as some limitations and complications. Overcoming these challenges and issues concerning the delivery of such tools to hematopoietic stem cells (HSCs) conserving their engrafting ability, may open the way to available curative approaches for SCD and other hemoglobinopathies
Autores principais:Draiblate, Beatriz Lopes
Assunto:Sickle cell anemia Hematopoietic stem cells Haemoglobin CRISPR Induced pluripotent stem cells Biologia Molecular
Ano:2020
País:Portugal
Tipo de documento:dissertação de mestrado
Tipo de acesso:acesso aberto
Instituição associada:Universidade de Lisboa
Idioma:inglês
Origem:Repositório da Universidade de Lisboa
Descrição
Resumo:Drepranocitosis (or sickle cell anemia - SCA) is a genetic hereditary disease that affects millions of people worldwide, bearing significant clinical features and a compromised prognosis with increased recurrences of crisis. Many treatments have been suggested to help dealing with sickle cell anemia, either by reducing and managing the consequences of the disease, or even by trying to solve it (bone marrow transplant). However, until date, there has not been developed a “perfect” therapeutic approach. Gene therapy has been used as the ultimate weapon to treat diseases whose cure cannot be achieved with traditional methods. CRISPR-Cas9 showed to be potentially safer and more efficient in treating SCD than other conventional gene therapies, which is presumed to be a result of the precision of the correction of this tool and the lack of use of viral vectors. Comparing with other available gene-editing techniques, namely zinc finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs), CRISPR/Cas9 offers some advantages, as well as some limitations and complications. Overcoming these challenges and issues concerning the delivery of such tools to hematopoietic stem cells (HSCs) conserving their engrafting ability, may open the way to available curative approaches for SCD and other hemoglobinopathies