Porous crystalline solids, including metal-organic frameworks (MOFs), covalent-organic frameworks (COFs), hydrogen-bonded organic frameworks (HOFs) and zeolites, have recently emerged as a promising class of materials in the field of gene therapy. Current gene therapeutic approaches aim to treat genetic disorders, cancer, and a wide range of diseases, including rare disorders of low incidence, through the delivery of nucleic acids (including DNA, mRNA, and siRNA) directly into target cells to modulate gene expression. However, the therapeutic potential of nucleic acids is severely limited by their intrinsic instability in vivo and by the multitude of biological barriers that hinder efficient cellular uptake and precise subcellular delivery. Recent studies highlight the growing utility of porous crystalline solids for nucleic acid delivery, as their intrinsic features allow for precise cargo encapsulation, surface functionalization, and controlled release. Despite advances, translating these materials into clinical settings remains constrained by challenges related to biocompatibility, targeted delivery, and safety, highlighting the need for deeper investigation across disciplines.

This Research Topic aims to provide a comprehensive overview of cutting-edge developments in leveraging porous crystalline solids for gene therapeutics. The primary objectives are to explore recent innovations in material design and nucleic acid delivery strategies, elucidate the relationships that define framework–nucleic acid interactions, and identify mechanisms by which these materials can facilitate efficient, safe, and targeted gene delivery. The Research Topic further seeks to bring together contributions from both fundamental and translational research, emphasizing multifunctionality, stimuli-responsiveness, and precision targeting in preclinical and emerging therapeutic applications. By fostering dialogue across materials chemistry, biomedical engineering, and clinical research, this collection will help address current barriers and chart paths toward clinical success.

The scope of this Research Topic is broad yet focused, encompassing foundational research through translational studies that harness porous crystalline solids for gene therapy. Reviews, original research articles, perspectives, and brief reports are welcome that advance our understanding of these materials or deepen insights into their application. To gather further insights in the multidisciplinary boundaries of materials science and gene therapy, we welcome articles addressing, but not limited to, the following themes:
• Fundamental studies on interactions between crystalline materials and nucleic acids
• Novel strategies for encapsulation, protection, and controlled release of genetic cargo
• Design and development of stimuli-responsive and multifunctional porous crystalline platforms
• Surface engineering for targeted and improved biodistribution in gene delivery
• Preclinical applications in oncology, genetic, and metabolic disorders
• Assessments of biocompatibility, biodegradability, and safety
• Integrative approaches connecting porous crystalline materials with complementary nanocarrier and delivery modalities

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Porous Crystalline Solids as Innovative Platforms for Nucleic Acid-Based Gene Therapeutics