DNA-Based Nanocarriers to Sequester Altered microRNAs in Cardiac Dysfunction

Postigo, Alejandro ; Hernández-Bellido, Natalia (Universidad de Zaragoza) ; Sánchez-Barat, Marcos (Universidad de Zaragoza) ; García-Mendívil, Laura ; Pueyo, Esther (Universidad de Zaragoza) ; del Barrio, Jesús (Universidad de Zaragoza) ; Hernández-Ainsa, Silvia ; Ordovás, Laura

Resumen: MicroRNAs (miRs) play a critical role in modulating gene expression across biological processes, including cardiac aging and disease. As such, miRs have demonstrated therapeutic potential in several cardiac conditions. Efficient delivery of miR therapies to cardiac tissue is crucial for effective gene therapy and DNA‐based nanocarriers (DNCs), based on Watson‐Crick‐Franklin highly specific base‐pair recognition, have emerged as a promising, biocompatible alternative to viral‐based methods. Here, DNCs designed to modulate miR levels as a potential treatment for cardiac dysfunction are presented. Specifically, the DNCs target miR‐24‐2, which inhibits SERCA2 gene. In humans, the reduction of SERCA2 activity is a hallmark of heart failure and is altered in cardiac aging. The assembled DNCs bearing anti‐miR‐24‐2‐5p sequences effectively restore intracellular levels of SERCA2 in a HEK293 cell model. The DNCs proper assembly is thoroughly verified, while their stability and miR‐capture ability are demonstrated in vitro. The DNCs exhibit successful internalization into HEK293 and modest uptake into human cardiomyocytes. SERCA2 restoration by DNCs is significantly influenced by the miR‐capture sequence layout, underscoring the importance of precise design for optimal biological outcomes. This study highlights the potential of DNCs in cardiac therapies, a previously unexplored avenue for addressing cardiac dysfunction.

Idioma: Inglés

DOI: 10.1002/adtp.202400247

Año: 2024

Publicado en: Advanced Therapeutics (2024), 2400247 [10 pp.]
ISSN: 2366-3987

Financiación: info:eu-repo/grantAgreement/ES/DGA/E47-23R
Financiación: info:eu-repo/grantAgreement/ES/DGA/LMP128_21
Financiación: info:eu-repo/grantAgreement/ES/DGA/T39-23R
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PCI2023-143390
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PCI2023-143438
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PID2022-139859OB-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN-AEI/PRTR-C17.I1
Financiación: info:eu-repo/grantAgreement/ES/MCINN/PID2020-113003GB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Química Orgánica (Dpto. Química Orgánica)
Área (Departamento): Área Teoría Señal y Comunicac. (Dpto. Ingeniería Electrón.Com.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

Dataset asociado: Supplementary Data for DNA-Based Nanocarriers to Sequester Altered microRNAs in Cardiac Dysfunction ( 10.5281/zenodo.13921161)