en Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله مروری Review Article <div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:10.5pt"><span style="line-height:115%"><span style="color:black">Adenoviral vectors (AdVs) represent one of the most extensively researched platforms in the realm of gene therapy, providing advantages such as high transduction efficiency, large transgene capacity, and broad tropism. This review provides a detailed and structured overview of AdVs, highlighting their biology, gene delivery mechanisms, clinical applications, and challenges limiting their broader therapeutic applicability. The study also explores recent progress in vector engineering, such as rare serotypes, capsid modifications, third-generation vectors, as well as strategies for immune modulation and toxicity reduction. AdVs are used in therapies for genetic disorders, oncology, and vaccinology, alongside innovations such as CRISPR-Cas9, nanotechnology, and artificial intelligence design. Nevertheless, persistent hurdles, including vector immunogenicity, hepatotoxicity, scalability, and the lack of durable expression, prevent widespread clinical use. This review consolidates current knowledge and presents a future perspective on how AdVs may evolve as powerful, adaptable, and precise tools in modern gene therapy. By contextualizing strengths and unresolved challenges, this work aims to give researchers and clinicians a balanced foundation for evaluating their future roles in translational medicine. </span></span></span></span></div> Adenoviridae, Genetic therapy, Oncolytic virotherapy, Transgene 16 35 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-6243-1&slc_lang=en&sid=1 Hamidreza Saber hamidreza.saber1382@gmail.com 0009-0007-7469-8068 Yes Department of Cellular and Molecular Biology, Faculty of Basic Sciences, Islamic Azad University of Ardabil Branch, Ardabil, Iran Zahra Mousavipour zahra.mpr.2003@gmail.com 0009-0009-9840-7792 No Department of Molecular Genetics and Development Biology, Faculty of Biology, University of Innsbruck, Innsbruck, Austria