Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion
Non-canonical functions of olfactory receptors, one of the largest families of GPCR receptors not confined to the olfactory system, include an intriguing role on hair physiology. Previous studies using odorant agonists of the Olfactory Receptor family 2 subfamily AT member 4 (OR2AT4) showed hair gro...
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Elsevier
2025-09-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253125001623 |
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| author | Manuel Mataix Nuria Illera Inés Hidalgo Maria del Carmen de Arriba Elena Martín Gerónimo Fernández Carlos González Fernando Larcher Victor M. González Marcela del Rio Francisco Jiménez Marta Carretero |
| author_facet | Manuel Mataix Nuria Illera Inés Hidalgo Maria del Carmen de Arriba Elena Martín Gerónimo Fernández Carlos González Fernando Larcher Victor M. González Marcela del Rio Francisco Jiménez Marta Carretero |
| author_sort | Manuel Mataix |
| collection | DOAJ |
| description | Non-canonical functions of olfactory receptors, one of the largest families of GPCR receptors not confined to the olfactory system, include an intriguing role on hair physiology. Previous studies using odorant agonists of the Olfactory Receptor family 2 subfamily AT member 4 (OR2AT4) showed hair growth stimulation. To develop more effective topical or systemic treatments for hair growth by specifically activating this receptor, it is crucial to identify new molecules with potent and well-defined activity. Here, we present a significant advancement in targeted therapeutic strategies for hair loss through the identification of a highly specific DNA aptamer targeting OR2AT4. The selected aptamer, designed as Ap.OR2AT4.17, effectively prolonged the anagen phase of hair growth cycle in a valuable preclinical human organ culture model. Importantly, the identified OR2AT4 aptamer was shown to be functional, leading to enhanced OR2AT4 expression in hair follicles, increased proliferation of hair matrix keratinocytes, and significant hair shaft elongation in organ-cultured human hair follicles. Notably, aptamer treatment also upregulated LL-37 and human β defensin-3 antimicrobial peptide expression, highlighting its role as a microbiota-modulating compound. These findings underscore the OR2AT4 aptamer’s potential as a novel, targeted therapy for hair loss disorders, marking a promising step forward in the field. |
| format | Article |
| id | doaj-art-99c09cd660a8466cbefe5f2d76eecf27 |
| institution | DOAJ |
| issn | 2162-2531 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj-art-99c09cd660a8466cbefe5f2d76eecf272025-08-20T02:42:34ZengElsevierMolecular Therapy: Nucleic Acids2162-25312025-09-0136310260810.1016/j.omtn.2025.102608Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotionManuel Mataix0Nuria Illera1Inés Hidalgo2Maria del Carmen de Arriba3Elena Martín4Gerónimo Fernández5Carlos González6Fernando Larcher7Victor M. González8Marcela del Rio9Francisco Jiménez10Marta Carretero11Epithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainEpithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, SpainUniversidad Carlos III de Madrid, ROR: https://ror.org/03ths8210, Departmento de Bioingeniería, Avenida de la Universidad, 30 (edificio Sabatini), 28911 Leganés (Madrid), SpainEpithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, SpainAptamer Group, IRYCIS-Hospital Ramón y Cajal, Madrid, SpainAptamer Group, IRYCIS-Hospital Ramón y Cajal, Madrid, SpainInstituto de Química Física Blas Cabrera, CSIC, Serrano 119, 28006 Madrid, SpainEpithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, SpainAptamer Group, IRYCIS-Hospital Ramón y Cajal, Madrid, SpainHealth Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain; Universidad Carlos III de Madrid, ROR: https://ror.org/03ths8210, Departmento de Bioingeniería, Avenida de la Universidad, 30 (edificio Sabatini), 28911 Leganés (Madrid), Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, SpainMediteknia Skin & Hair Lab, Gran Canaria, Spain; Universidad Fernando Pessoa Canarias, Gran Canaria, SpainEpithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain; Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain; Corresponding author: Marta Carretero, Epithelial Biomedicine Division, Centre for Energy, Environment and Technology Research (CIEMAT), Madrid, Spain.Non-canonical functions of olfactory receptors, one of the largest families of GPCR receptors not confined to the olfactory system, include an intriguing role on hair physiology. Previous studies using odorant agonists of the Olfactory Receptor family 2 subfamily AT member 4 (OR2AT4) showed hair growth stimulation. To develop more effective topical or systemic treatments for hair growth by specifically activating this receptor, it is crucial to identify new molecules with potent and well-defined activity. Here, we present a significant advancement in targeted therapeutic strategies for hair loss through the identification of a highly specific DNA aptamer targeting OR2AT4. The selected aptamer, designed as Ap.OR2AT4.17, effectively prolonged the anagen phase of hair growth cycle in a valuable preclinical human organ culture model. Importantly, the identified OR2AT4 aptamer was shown to be functional, leading to enhanced OR2AT4 expression in hair follicles, increased proliferation of hair matrix keratinocytes, and significant hair shaft elongation in organ-cultured human hair follicles. Notably, aptamer treatment also upregulated LL-37 and human β defensin-3 antimicrobial peptide expression, highlighting its role as a microbiota-modulating compound. These findings underscore the OR2AT4 aptamer’s potential as a novel, targeted therapy for hair loss disorders, marking a promising step forward in the field.http://www.sciencedirect.com/science/article/pii/S2162253125001623MT: Oligonucleotides: Therapies and Applicationsalopeciaolfactory receptorOR2AT4aptamerantimicrobial peptides |
| spellingShingle | Manuel Mataix Nuria Illera Inés Hidalgo Maria del Carmen de Arriba Elena Martín Gerónimo Fernández Carlos González Fernando Larcher Victor M. González Marcela del Rio Francisco Jiménez Marta Carretero Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion Molecular Therapy: Nucleic Acids MT: Oligonucleotides: Therapies and Applications alopecia olfactory receptor OR2AT4 aptamer antimicrobial peptides |
| title | Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion |
| title_full | Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion |
| title_fullStr | Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion |
| title_full_unstemmed | Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion |
| title_short | Targeting olfactory receptor OR2AT4: An innovative aptamer-based treatment for hair growth promotion |
| title_sort | targeting olfactory receptor or2at4 an innovative aptamer based treatment for hair growth promotion |
| topic | MT: Oligonucleotides: Therapies and Applications alopecia olfactory receptor OR2AT4 aptamer antimicrobial peptides |
| url | http://www.sciencedirect.com/science/article/pii/S2162253125001623 |
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