Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference
Molecular therapy uses nucleic acid-based therapeutics agents and becomes a promising alternative for disease conditions unresponsive to traditional pharmaceutical approaches. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are two well-known strategies used to modulate gene ex...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2025.1525373/full |
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| author | Olga Golounina Ildar Minniakhmetov Ramil Salakhov Rita Khusainova Ekaterina Zakharova Igor Bychkov Natalia Mokrysheva |
| author_facet | Olga Golounina Ildar Minniakhmetov Ramil Salakhov Rita Khusainova Ekaterina Zakharova Igor Bychkov Natalia Mokrysheva |
| author_sort | Olga Golounina |
| collection | DOAJ |
| description | Molecular therapy uses nucleic acid-based therapeutics agents and becomes a promising alternative for disease conditions unresponsive to traditional pharmaceutical approaches. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are two well-known strategies used to modulate gene expression. RNA-targeted therapy can precisely modulate the function of target RNA with minimal off-target effects and can be rationally designed based on sequence data. ASOs and siRNA-based drugs have unique capabilities for using in target groups of patients or can be tailored as patient-customized N-of-1 therapeutic approach. Antisense therapy can be utilized not only for the treatment of monogenic diseases but also holds significant promise for addressing polygenic and complex diseases by targeting key genes and molecular pathways involved in disease pathogenesis. In the context of endocrine disorders, molecular therapy is particularly effective in modulating pathogenic mechanisms such as defective insulin signaling, beta-cell dysfunction and hormonal imbalances. Furthermore, siRNA and ASOs have the ability to downregulate overactive signaling pathways that contribute to complex, non-monogenic endocrine disorders, thereby addressing these conditions at their molecular origin. ASOs are also being studied worldwide as unique candidates for developing therapies for N-of-1 therapies. The sequence-specific ASOs binding provides exceptional accuracy in N-of-1 approaches, when the oligonucleotide can be targeted to a patient’s exact mutant sequence. In this review we focus on diseases of the endocrine system and discuss potential RNA-targeted therapeutic opportunities in diabetes mellitus, including monogenic beta cell diabetes, and obesity, including syndrome obesity and monogenic obesity, as well as in non-monogenic or complex endocrine disorders. We also provide an overview of currently developed and available antisense molecules, and describe potentials of antisense-based therapeutics for the treatment of rare and «ultrarare» endocrine diseases. |
| format | Article |
| id | doaj-art-7c23b8de44014277ad6f4d63b37cfc06 |
| institution | Kabale University |
| issn | 1664-2392 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj-art-7c23b8de44014277ad6f4d63b37cfc062025-01-29T05:21:13ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-01-011610.3389/fendo.2025.15253731525373Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interferenceOlga Golounina0Ildar Minniakhmetov1Ramil Salakhov2Rita Khusainova3Ekaterina Zakharova4Igor Bychkov5Natalia Mokrysheva6Department of Clinical Endocrinology, Endocrinology Research Centre, Moscow, RussiaLaboratory of Genomic Medicine, Endocrinology Research Centre, Moscow, RussiaLaboratory of Genomic Medicine, Endocrinology Research Centre, Moscow, RussiaLaboratory of Genomic Medicine, Endocrinology Research Centre, Moscow, RussiaSelective Screening Laboratory, Research Centre for Medical Genetics, Moscow, RussiaLaboratory of Experimental Gene Therapy for Inherited Metabolic Diseases, Research Centre for Medical Genetics, Moscow, RussiaDepartment of Clinical Endocrinology, Endocrinology Research Centre, Moscow, RussiaMolecular therapy uses nucleic acid-based therapeutics agents and becomes a promising alternative for disease conditions unresponsive to traditional pharmaceutical approaches. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are two well-known strategies used to modulate gene expression. RNA-targeted therapy can precisely modulate the function of target RNA with minimal off-target effects and can be rationally designed based on sequence data. ASOs and siRNA-based drugs have unique capabilities for using in target groups of patients or can be tailored as patient-customized N-of-1 therapeutic approach. Antisense therapy can be utilized not only for the treatment of monogenic diseases but also holds significant promise for addressing polygenic and complex diseases by targeting key genes and molecular pathways involved in disease pathogenesis. In the context of endocrine disorders, molecular therapy is particularly effective in modulating pathogenic mechanisms such as defective insulin signaling, beta-cell dysfunction and hormonal imbalances. Furthermore, siRNA and ASOs have the ability to downregulate overactive signaling pathways that contribute to complex, non-monogenic endocrine disorders, thereby addressing these conditions at their molecular origin. ASOs are also being studied worldwide as unique candidates for developing therapies for N-of-1 therapies. The sequence-specific ASOs binding provides exceptional accuracy in N-of-1 approaches, when the oligonucleotide can be targeted to a patient’s exact mutant sequence. In this review we focus on diseases of the endocrine system and discuss potential RNA-targeted therapeutic opportunities in diabetes mellitus, including monogenic beta cell diabetes, and obesity, including syndrome obesity and monogenic obesity, as well as in non-monogenic or complex endocrine disorders. We also provide an overview of currently developed and available antisense molecules, and describe potentials of antisense-based therapeutics for the treatment of rare and «ultrarare» endocrine diseases.https://www.frontiersin.org/articles/10.3389/fendo.2025.1525373/fullendocrine diseasesmolecular therapyRNA therapeuticsantisense oligonucleotides (ASOs)small interfering RNA (siRNA)N-of-1 |
| spellingShingle | Olga Golounina Ildar Minniakhmetov Ramil Salakhov Rita Khusainova Ekaterina Zakharova Igor Bychkov Natalia Mokrysheva Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference Frontiers in Endocrinology endocrine diseases molecular therapy RNA therapeutics antisense oligonucleotides (ASOs) small interfering RNA (siRNA) N-of-1 |
| title | Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference |
| title_full | Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference |
| title_fullStr | Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference |
| title_full_unstemmed | Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference |
| title_short | Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference |
| title_sort | pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and rna interference |
| topic | endocrine diseases molecular therapy RNA therapeutics antisense oligonucleotides (ASOs) small interfering RNA (siRNA) N-of-1 |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2025.1525373/full |
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