Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease
Huntington’s disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington’s Disease are caused by a pathological increase in the number of Cytokine-Adenine-G...
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2024-12-01
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| author | Sergio Adrian Ocampo-Ortega Vivany Maydel Sierra-Sanchez Citlali Margarita Blancas-Napoles Asdrúbal González-Carteño Elvia Mera-Jiménez Martha Edith Macías-Pérez Adriana Hernandez-Guerra Rodrigo Romero-Nava Fengyang Huang Enrique Hong Santiago Villafaña |
| author_facet | Sergio Adrian Ocampo-Ortega Vivany Maydel Sierra-Sanchez Citlali Margarita Blancas-Napoles Asdrúbal González-Carteño Elvia Mera-Jiménez Martha Edith Macías-Pérez Adriana Hernandez-Guerra Rodrigo Romero-Nava Fengyang Huang Enrique Hong Santiago Villafaña |
| author_sort | Sergio Adrian Ocampo-Ortega |
| collection | DOAJ |
| description | Huntington’s disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington’s Disease are caused by a pathological increase in the number of Cytokine-Adenine-Guanine (CAG) repeats on the first exon of the Huntingtin gene, which causes a protein to have an excessive number of glutamine residues; this alteration leads to a change in the protein’s conformation and function. Therefore, the purpose of this work was to design, synthesize and evaluate an antisense oligonucleotide (ASO; 95 nucleotides) HTT 90-5 directed to the Huntingtin CAG repeats in primary leukocyte culture cells from a patient with Huntington’s Disease; approximately 500,000 leukocytes per well extracted from venous blood were used, to which 100 pMol of ASO were administered, and the expression of Huntingtin was subsequently evaluated at 72 h by RT-PCR. Our results showed that the administration of the HTT 90-5 antisense decreased the expression of Huntingtin mRNA in the primary culture leukocyte cells from our patient. These results suggest that the use of long antisense targeting the CAG Huntingtin cluster may be an option to decrease the expression of Huntingtin and probably could be adjusted depending on the number of CAG repeats in the cluster. |
| format | Article |
| id | doaj-art-7c78d0d712be4de19fdfb7d4ac3efab2 |
| institution | Kabale University |
| issn | 2075-1729 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj-art-7c78d0d712be4de19fdfb7d4ac3efab22024-12-27T14:36:04ZengMDPI AGLife2075-17292024-12-011412160710.3390/life14121607Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s DiseaseSergio Adrian Ocampo-Ortega0Vivany Maydel Sierra-Sanchez1Citlali Margarita Blancas-Napoles2Asdrúbal González-Carteño3Elvia Mera-Jiménez4Martha Edith Macías-Pérez5Adriana Hernandez-Guerra6Rodrigo Romero-Nava7Fengyang Huang8Enrique Hong9Santiago Villafaña10Laboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Cultivo Celular, Neurobiología y Conducta, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Cultivo Celular, Neurobiología y Conducta, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoLaboratorio de Investigación en Obesidad y Asma, Hospital Infantil de Mexico “Federico Gómez”, Ciudad de Mexico 06720, MexicoDepartamento de Neurofarmacobiología, Centro de Investigación y de Estudios Avanzados, Ciudad de Mexico 14330, MexicoLaboratorio de Terapia Génica Experimental, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, MexicoHuntington’s disease is a genetic disorder characterized by progressive neuronal cell damage in some areas of the brain; symptoms are commonly associated with chorea, rigidity and dystonia. The symptoms in Huntington’s Disease are caused by a pathological increase in the number of Cytokine-Adenine-Guanine (CAG) repeats on the first exon of the Huntingtin gene, which causes a protein to have an excessive number of glutamine residues; this alteration leads to a change in the protein’s conformation and function. Therefore, the purpose of this work was to design, synthesize and evaluate an antisense oligonucleotide (ASO; 95 nucleotides) HTT 90-5 directed to the Huntingtin CAG repeats in primary leukocyte culture cells from a patient with Huntington’s Disease; approximately 500,000 leukocytes per well extracted from venous blood were used, to which 100 pMol of ASO were administered, and the expression of Huntingtin was subsequently evaluated at 72 h by RT-PCR. Our results showed that the administration of the HTT 90-5 antisense decreased the expression of Huntingtin mRNA in the primary culture leukocyte cells from our patient. These results suggest that the use of long antisense targeting the CAG Huntingtin cluster may be an option to decrease the expression of Huntingtin and probably could be adjusted depending on the number of CAG repeats in the cluster.https://www.mdpi.com/2075-1729/14/12/1607CAG clusterHuntington’s diseaseHuntingtinlong antisense oligonucleotide |
| spellingShingle | Sergio Adrian Ocampo-Ortega Vivany Maydel Sierra-Sanchez Citlali Margarita Blancas-Napoles Asdrúbal González-Carteño Elvia Mera-Jiménez Martha Edith Macías-Pérez Adriana Hernandez-Guerra Rodrigo Romero-Nava Fengyang Huang Enrique Hong Santiago Villafaña Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease Life CAG cluster Huntington’s disease Huntingtin long antisense oligonucleotide |
| title | Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease |
| title_full | Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease |
| title_fullStr | Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease |
| title_full_unstemmed | Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease |
| title_short | Evaluation of an Antisense Oligonucleotide Targeting CAG Repeats: A Patient-Customized Therapy Study for Huntington’s Disease |
| title_sort | evaluation of an antisense oligonucleotide targeting cag repeats a patient customized therapy study for huntington s disease |
| topic | CAG cluster Huntington’s disease Huntingtin long antisense oligonucleotide |
| url | https://www.mdpi.com/2075-1729/14/12/1607 |
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