Nucleic acid (NA)-based biopharmaceuticals have emerged as promising therapeutic modalities. NA therapeutics are a diverse class of RNA and DNA and include antisense oligonucleotides, siRNA, miRNA, mRNA, small activating RNA, and gene therapies. Meanwhile, NA therapeutics have posed significant stability and delivery challenges and are expensive. This article discusses the challenges and opportunities for achieving stable formulations of NAs with novel drug delivery systems (DDSs). Here we review the current progress in the stability issues and the significance of novel DDSs associated with NA-based biopharmaceuticals, as well as mRNA vaccines. We also highlight the European Medicines Agency (EMA) and US Food and Drug Administration (FDA)-approved NA-based therapeutics with their formulation profiles. NA therapeutics could impact future markets if the remaining challenges and requirements are addressed. Regardless of the limited information available for NA therapeutics, reviewing and collating the relevant facts and figures generates a precious resource for formulation experts familiar with the NA therapeutics’ stability profile, their delivery challenges, and regulatory acceptance.

Microneedle technology revolutionizes ocular drug delivery by addressing challenges in treating ocular diseases. This review explores its potential impact, recent advancements, and clinical uses. This minimally invasive technique offers precise control of drug delivery to the eye, with various microneedle types showing the potential to penetrate barriers in the cornea and sclera, ensuring effective drug delivery. Recent advancements have improved safety and efficacy, offering sustained and controlled drug delivery for conditions like age-related macular degeneration and glaucoma. While promising, challenges such as regulatory barriers and long-term biocompatibility persist. Overcoming these through interdisciplinary research is crucial. Ultimately, microneedle drug delivery presents a revolutionary method with the potential to significantly enhance ocular disease treatment, marking a new era in eye care.

Proteins are vital for the regulation of several cellular functions, including the synthesis of structural components. The change in environmental conditions will impact conformational stability and result in aggregation. Protein aggregation involves different states of proteins, like nonnative, unfolded, and native states, which make them complex processes. The proper understanding of protein aggregation pathways involving the role of thermodynamically unfavoured lag phase, soluble protofibrils triggered polymerization through an exponential phase, and depleted free monomers owing to the saturation phase resulted in the leveling off of the polymerization process. The aggregated therapeutic proteins can induce deleterious immune responses in patients, and control of the aggregation is essential for better therapeutic protein stability and targeting with the help of stable protein structures and function. Protein–protein interactions (PPIs) are important for protein stability, aggregation rate, and solubility, while advanced computational and biophysical methods have been developed to characterize therapeutic protein aggregation better. Hence, an effective strategy for controlling, monitoring, and reproducing protein aggregation propensities of the polypeptide chains is required. An in-depth understanding of protein aggregation mechanisms, characterization, and combat strategies will counter the issues of protein aggregation. It will also reduce the cost of the product, time constraints, stable & effective product availability, and potential immunogenicity. Graphical Abstract

Cancer has rapidly emerged as a leading global cause of premature mortality, with significant economic implications projected to reach USD 25.2 trillion from 2020 to 2050. Among the various types of cancer, primary bone cancers, though uncommon, are projected to see nearly 4000 new cases diagnosed in the United States in 2024. The complexity of treating bone cancer arises from its rarity, diversity, and the challenges associated with surgical interventions, metastatic spread, and post-operative complications. Advancements in bone tissue engineering (BTE) have introduced innovative therapeutic approaches to promote bone regeneration and address tumor recurrence. This interdisciplinary field integrates biomaterials, scaffolds, and gene therapy, utilizing technologies such as 3D bioprinting to create custom scaffolds that facilitate cellular activities essential for tissue regeneration. Recent developments in biodegradable, bioactive materials aim to enhance the biocompatibility and effectiveness of scaffolds, while nanotechnology presents promising avenues for targeted drug delivery and improved therapeutic outcomes. This review outlines the current landscape of BTE, highlighting scaffold fabrication techniques, the advantages of incorporating stem cell and gene therapies, and future directions, including the integration of artificial intelligence in scaffold design for personalized medicine in orthopedic oncology. This work underscores the necessity for ongoing research and innovation, aiming to improve therapeutic strategies specifically designed to address the unique challenges posed by bone sarcomas and metastatic cancers.

Several severe disorders, such as inherited diseases (e.g. cystic fibrosis and beta thalassemia), genetic diseases (e.g. malignant tumors and diabetes), and infectious diseases (e.g. HIV) are pose significant challenges to human health. Over the past few decades, researchers have been working on gene therapies, and currently, terrible dreams have come true. To date, the Food and Drug Administration (FDA) has approved multiple gene therapies such as Kynamro for familial hypercholesterolaemia, Exondys51 for duchenne muscular dystrophy, Spinraza for spinal muscular atrophy, etc., rest for cancer, infectious diseases, and rare diseases. The authors have summarized recent advances in gene therapy, its background, molecular basis (e.g. viral and non-viral vectors), gene-editing techniques (e.g. CRISPR/Cas9, TALEN, ZFN), and its foremost applications in severe disorders, such as cancer, monogenic disorders (e.g. spinal muscular atrophy), polygenic disorders (e.g. autism), neurogenic disorders (e.g. Parkinson disease and Alzheimer's disease), and infectious diseases (e.g. HIV). In addition, we explored the major challenges faced by gene therapies during targeted delivery, immunogenicity, efficacy, and safety. To date, most of the promising approaches, such as different vectors, target cell populations, and both in vivo and ex vivo have paved the foundation for applications of gene therapies. Additionally, advances in enhancing the immune system that would certainly lower the healthcare costs. This review highlights the translatory potential of gene therapy in revolutionizing the treatment landscape for severe disorders.

Copper-based metal organic frameworks (Cu-MOFs) represent a highly versatile family of porous crystalline materials valued for their tunable structures, redox-active Cu centers, and inherent biodegradability, which collectively increase their therapeutic and technological potential. This review provides an integrated overview of recent progress in synthetic approaches ranging from solvothermal and mechanochemical techniques to more sustainable, scalable green processes and emphasizes how precise control over coordination chemistry, defect formation, and surface engineering governs their physicochemical performance. Major biomedical advancements are highlighted, particularly their role as both drug delivery platforms and active therapeutic agents capable of generating reactive oxygen species for chemodynamic therapy, supporting synergistic phototherapies, and exerting antimicrobial effects, with innovations in stimuli-responsive designs and biomimetic modifications improving stability and targeting under physiological conditions. Additionally, the increasing importance of Cu-MOFs in catalysis, energy storage, and environmental remediation underscores their wide-ranging industrial significance. Nonetheless, challenges such as ensuring long-term biosafety, maintaining stability in biological environments, and achieving reproducible large-scale production continue to limit clinical translation. Future progress will rely on predictive design tools, deeper structure–function understanding, and standardized biological assessments. Overall, Cu-MOFs stand at the interface of materials science and biomedicine, with ongoing innovations poised to drive their evolution from promising laboratory systems into impactful real-world applications.