Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid‐based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.

Macrophages (MCs) are present in all tissues, not only supporting homeostasis, but also playing an important role in organogenesis, post-injury regeneration, and diseases. They are a heterogeneous cell population due to their origin, tissue specificity, and polarization in response to aggression factors, depending on environmental cues. Thus, as pro-inflammatory M1 phagocytic MCs, they contribute to tissue damage and even fibrosis, but the anti-inflammatory M2 phenotype participates in repairing processes and wound healing through a molecular interplay with most cells in adult stem cell niches. In this review, we emphasize MC phenotypic heterogeneity in health and disease, highlighting their systemic and systematic contribution to tissue homeostasis and repair. Unraveling the intervention of both resident and migrated MCs on the behavior of stem cells and the regulation of the stem cell niche is crucial for opening new perspectives for novel therapeutic strategies in different diseases.

Despite recent advances in targeted cancer therapies, drug resistance remains an important setback in tumor control. Understanding the complex mechanisms involved in both innate and acquired drug resistance represents the first step in discovering novel therapeutic agents. Because of its importance in tumorigenesis, progression, and metastasis, lipid metabolism is increasingly garnering attention. CD36 is a membrane receptor at the top of the signaling cascade that transports lipids. Its expression has been repeatedly presented as an unfavorable prognostic factor for various tumor types, raising the question: could CD36 be a critical factor in cancer treatment resistance? In our review, we set out to explore the most prominent studies on the implication of CD36 in resistance to platinum-based drugs and other adjuvant cancer therapies in solid and haematological neoplasia. Moreover, we provide an overview of the latest anti-CD36 cancer therapies, thus opening new perspectives for future personalized medicine.

The muscular dystrophies are a heterogeneous group of genetically inherited diseases characterized by muscle weakness and progressive wasting, which can cause premature death in severe forms. Although >30 years have passed since the identification of the first protein involved in a type of muscular dystrophy, there is no effective treatment for these disabling disorders. In the last decade, several novel therapeutic approaches have been developed and investigated as promising therapeutic approaches aimed to ameliorate the dystrophic phenotype either by restoring dystrophin expression or by compensating for dystrophin deficiency. Concurrently, with the development of therapeutic approaches, in addition to naturally occurring animal models, a wide range of genetically engineered animal models has been generated. The use of animals as models of muscular dystrophies has greatly improved the understanding of the pathogenicity of these diseases and has proven useful in gene therapy studies. In this review, we summarize these latest innovative therapeutic approaches to muscular dystrophies and the usefulness of the various most common experimental animal models.

Although they are considered rare disorders, muscular dystrophies have a strong impact on people’s health. Increased disease severity with age, frequently accompanied by the loss of ability to walk in some people, and the lack of treatment, have directed the researchers towards the development of more effective therapeutic strategies aimed to improve the quality of life and life expectancy, slow down the progression, and delay the onset or convert a severe phenotype into a milder one. Improved understanding of the complex pathology of these diseases together with the tremendous advances in molecular biology technologies has led to personalized therapeutic procedures. Different approaches that are currently under extensive investigation require more efficient, sensitive, and less invasive methods. Due to its remarkable analytical sensitivity, droplet digital PCR has become a promising tool for accurate measurement of biomarkers that monitor disease progression and quantification of various therapeutic efficiency and can be considered a tool for non-invasive prenatal diagnosis and newborn screening. Here, we summarize the recent applications of droplet digital PCR in muscular dystrophy research and discuss the factors that should be considered to get the best performance with this technology.

In aged muscle, satellite cells’ symmetric and asymmetric divisions are impaired, and intrinsic and extrinsic complex mechanisms govern these processes. This review presents many updated aspects regarding muscle stem cells’ fate in normal and aging conditions. The balance between self-renewal and commitment divisions contributes to muscle regeneration, muscle homeostasis, aging, and disease. Stimulating muscle regeneration in aging could be a therapeutic target, but there is still a need to understand the many mechanisms that influence each other in satellite cells and their niche. We highlight here the general outlines regarding satellite cell divisions, the primary markers present in muscle stem cells, the aging aspects concerning signaling pathways involved in symmetric/asymmetric divisions, the regenerative capacity of satellite cells and their niche alteration in senescent muscle, genetics and epigenetics mechanisms implied in satellite cells aging and exercise effect on muscle regeneration in the elderly.