Molecular therapy uses nucleic acid-based therapeutics agents and becomes a promising alternative for disease conditions unresponsive to traditional pharmaceutical approaches. Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are two well-known strategies used to modulate gene expression. RNA-targeted therapy can precisely modulate the function of target RNA with minimal off-target effects and can be rationally designed based on sequence data. ASOs and siRNA-based drugs have unique capabilities for using in target groups of patients or can be tailored as patient-customized N-of-1 therapeutic approach. Antisense therapy can be utilized not only for the treatment of monogenic diseases but also holds significant promise for addressing polygenic and complex diseases by targeting key genes and molecular pathways involved in disease pathogenesis. In the context of endocrine disorders, molecular therapy is particularly effective in modulating pathogenic mechanisms such as defective insulin signaling, beta-cell dysfunction and hormonal imbalances. Furthermore, siRNA and ASOs have the ability to downregulate overactive signaling pathways that contribute to complex, non-monogenic endocrine disorders, thereby addressing these conditions at their molecular origin. ASOs are also being studied worldwide as unique candidates for developing therapies for N-of-1 therapies. The sequence-specific ASOs binding provides exceptional accuracy in N-of-1 approaches, when the oligonucleotide can be targeted to a patient’s exact mutant sequence. In this review we focus on diseases of the endocrine system and discuss potential RNA-targeted therapeutic opportunities in diabetes mellitus, including monogenic beta cell diabetes, and obesity, including syndrome obesity and monogenic obesity, as well as in non-monogenic or complex endocrine disorders. We also provide an overview of currently developed and available antisense molecules, and describe potentials of antisense-based therapeutics for the treatment of rare and «ultrarare» endocrine diseases.

Endogenous Cushing’s syndrome (CS) is a rare neuroendocrine disorder characterized by either secondary cortisol increases due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor (Cushing’s disease (CD)), an ACTH-secreting neuroendocrine tumor (NET) of non-pituitary origin (ectopic ACTH syndrome (EAS)), or by the primarily adrenal autonomous overproduction of cortisol

Neuroendocrine neoplasms (NENs) represent a heterogeneous group of malignancies. In metastatic and progressive forms, standard therapies are often ineffective. CAR-T therapy, which has demonstrated remarkable efficacy in hematologic malignancies, is considered a promising approach for NEN treatment, despite significant barriers inherent to solid tumors. This review aims to comprehensively analyze and systematize current scientific data on the development of CAR-T therapy for NENs of various origins. It focuses on relevant molecular targets, preclinical findings demonstrating the efficacy and safety profiles of CAR-T cells directed against potential targets, and the current status of early-phase (I/II) clinical trials for CAR-T therapy in NENs. The review examines major barriers to CAR-T therapy in solid tumors, including NENs, and presents innovative strategies to overcome them. Further research and clinical trials focusing on therapy personalization, enhanced safety and efficacy, and the development of combination approaches are essential for the successful integration of CAR-T therapy into clinical practice and for improving outcomes in patients with treatment-refractory NENs.