Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management
Multiple sclerosis (MS) is a chronic autoimmune illness characterized by demyelination, neurodegeneration, and inflammation in the central nervous system. The AXL gene, which codes for a receptor tyrosine kinase, has emerged as a promising therapeutic target due to its involvement in neuroinflammati...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1548269/full |
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| author | Bhargav Shreevatsa Bhargav Shreevatsa Abhigna Nagaraj Chandan Dharmashekar Anisha Jain Bhavana Harendra Siddesh V. Siddalingegowda Haneen A. Al-Mazroua Sheikh F. Ahmad Shashanka K. Prasad Chandrashekar Srinivasa Chandan Shivamallu Shiva Prasad Kollur |
| author_facet | Bhargav Shreevatsa Bhargav Shreevatsa Abhigna Nagaraj Chandan Dharmashekar Anisha Jain Bhavana Harendra Siddesh V. Siddalingegowda Haneen A. Al-Mazroua Sheikh F. Ahmad Shashanka K. Prasad Chandrashekar Srinivasa Chandan Shivamallu Shiva Prasad Kollur |
| author_sort | Bhargav Shreevatsa |
| collection | DOAJ |
| description | Multiple sclerosis (MS) is a chronic autoimmune illness characterized by demyelination, neurodegeneration, and inflammation in the central nervous system. The AXL gene, which codes for a receptor tyrosine kinase, has emerged as a promising therapeutic target due to its involvement in neuroinflammation and oligodendrocyte dysfunction. In the current study, we employed in silico techniques to design Antisense Oligonucleotides (ASOs) that selectively target AXL gene transcripts to modulate AXL expression and mitigate MS pathology. Three ASOs, A1, A2, and A3, were designed to specifically target the 5′ untranslated region (5′UTR) and coding region of the AXL gene transcripts. The ASOs were optimized with a focus on stability, binding affinity, and specificity towards AXL mRNA while minimizing off-target effects. To investigate ASO-mRNA interactions and gauge their ability to alter AXL expression, Molecular Docking was performed. Our analyses showed that A1, A2, and A3 had substantial interactions with AXL mRNA, with binding affinities of −9.5 kcal/mol, −10.8 kcal/mol, and −10.6 kcal/mol, respectively. The targeting of AXL gene transcripts through ASOs shows promise in reducing MS symptoms. Precision ASO-based therapies could effectively manage MS by targeting the essential pathways involved in the disease. ASOs provide a highly targeted approach for treating MS and offer a precise therapeutic strategy for this debilitating condition. The study lays the groundwork for future in vitro and in vivo studies to confirm the therapeutic potential of these ASOs for the treatment of MS. |
| format | Article |
| id | doaj-art-d4696b9c5fdd434f903e54ab7c534e33 |
| institution | Kabale University |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj-art-d4696b9c5fdd434f903e54ab7c534e332025-02-05T07:32:38ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-02-011310.3389/fchem.2025.15482691548269Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment managementBhargav Shreevatsa0Bhargav Shreevatsa1Abhigna Nagaraj2Chandan Dharmashekar3Anisha Jain4Bhavana Harendra5Siddesh V. Siddalingegowda6Haneen A. Al-Mazroua7Sheikh F. Ahmad8Shashanka K. Prasad9Chandrashekar Srinivasa10Chandan Shivamallu11Shiva Prasad Kollur12Department of Microbiology, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, Columbia, SC, United StatesDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Microbiology, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Microbiology, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Microbiology, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Microbiology, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, IndiaDepartment of Studies in Biotechnology, Davangere University, Davangere, Karnataka, IndiaDepartment of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru, IndiaSchool of Physical Sciences, Amrita Vishwa Vidyapeetham, Mysuru, IndiaMultiple sclerosis (MS) is a chronic autoimmune illness characterized by demyelination, neurodegeneration, and inflammation in the central nervous system. The AXL gene, which codes for a receptor tyrosine kinase, has emerged as a promising therapeutic target due to its involvement in neuroinflammation and oligodendrocyte dysfunction. In the current study, we employed in silico techniques to design Antisense Oligonucleotides (ASOs) that selectively target AXL gene transcripts to modulate AXL expression and mitigate MS pathology. Three ASOs, A1, A2, and A3, were designed to specifically target the 5′ untranslated region (5′UTR) and coding region of the AXL gene transcripts. The ASOs were optimized with a focus on stability, binding affinity, and specificity towards AXL mRNA while minimizing off-target effects. To investigate ASO-mRNA interactions and gauge their ability to alter AXL expression, Molecular Docking was performed. Our analyses showed that A1, A2, and A3 had substantial interactions with AXL mRNA, with binding affinities of −9.5 kcal/mol, −10.8 kcal/mol, and −10.6 kcal/mol, respectively. The targeting of AXL gene transcripts through ASOs shows promise in reducing MS symptoms. Precision ASO-based therapies could effectively manage MS by targeting the essential pathways involved in the disease. ASOs provide a highly targeted approach for treating MS and offer a precise therapeutic strategy for this debilitating condition. The study lays the groundwork for future in vitro and in vivo studies to confirm the therapeutic potential of these ASOs for the treatment of MS.https://www.frontiersin.org/articles/10.3389/fchem.2025.1548269/fullAXL geneantisense oligonucleotidesmultiple sclerosisneurodegeneration inflammationtherapeutics |
| spellingShingle | Bhargav Shreevatsa Bhargav Shreevatsa Abhigna Nagaraj Chandan Dharmashekar Anisha Jain Bhavana Harendra Siddesh V. Siddalingegowda Haneen A. Al-Mazroua Sheikh F. Ahmad Shashanka K. Prasad Chandrashekar Srinivasa Chandan Shivamallu Shiva Prasad Kollur Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management Frontiers in Chemistry AXL gene antisense oligonucleotides multiple sclerosis neurodegeneration inflammation therapeutics |
| title | Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management |
| title_full | Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management |
| title_fullStr | Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management |
| title_full_unstemmed | Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management |
| title_short | Exploring precision therapeutics: computational design of antisense oligonucleotides targeting AXL gene transcripts in multiple sclerosis treatment management |
| title_sort | exploring precision therapeutics computational design of antisense oligonucleotides targeting axl gene transcripts in multiple sclerosis treatment management |
| topic | AXL gene antisense oligonucleotides multiple sclerosis neurodegeneration inflammation therapeutics |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1548269/full |
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