RT Journal Article T1 Dynamic Covalent Boronate Chemistry Accelerates the Screening of Polymeric Gene Delivery Vectors via In Situ Complexation of Nucleic Acids A1 Delgado González, Bruno A1 López-Blanco, Roi A1 Parcero Bouzas, Samuel A1 Barreiro Piñeiro, Natalia A1 García Abuín, Lucas A1 Fernández Megía, Eduardo K1 Aromatic compounds K1 Gene delivery K1 Gene therapy K1 Hydrocarbons K1 Nucleic acids AB Gene therapy provides exciting new therapeutic opportunities beyond the reach of traditional treatments. Despite the tremendous progress of viral vectors, their high cost, complex manufacturing, and side effects have encouraged the development of nonviral alternatives, including cationic polymers. However, these are less efficient in overcoming cellular barriers, resulting in lower transfection efficiencies. Although the exquisite structural tunability of polymers might be envisaged as a versatile tool for improving transfection, the need to fine-tune several structural parameters represents a bottleneck in current screening technologies. By taking advantage of the fast-forming and strong boronate ester bond, an archetypal example of dynamic covalent chemistry, a highly adaptable gene delivery platform is presented, in which the polycation synthesis and pDNA complexation occur in situ. The robustness of the strategy entitles the simultaneous evaluation of several structural parameters at will, enabling the accelerated screening and adaptive optimization of lead polymeric vectors using dynamic covalent libraries PB ACS SN 0002-7863 YR 2024 FD 2024-06-12 LK http://hdl.handle.net/10347/34876 UL http://hdl.handle.net/10347/34876 LA eng NO J. Am. Chem. Soc. 2024, 146, 25, 17211–17219 NO This work was supported by grant PID2021-127684OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by ERDF “A way of making Europe”. The authors also thank the financial support from Xunta de Galicia (ED431C 2022/21, and Centro de Investigación do Sistema Universitario de Galicia accreditation 2023-2027, ED431G 2023/03) and the European Union (European Regional Development Fund─ERDF). B.D.G. thanks Xunta de Galicia for a predoctoral grant DS Minerva RD 23 abr 2026