RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the use of these strategies and future directions of oral siRNA delivery strategies.
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http://dx.doi.org/10.3390/pharmaceutics14091969 | DOI Listing |
Acta Biomater
December 2024
Lingang Laboratory, Shanghai 200031, China. Electronic address:
Triple-negative breast cancer (TNBC) has been a clinical challenge due to its high recurrence and metastasis rates. Chemotherapy remains the primary treatment for TNBC after surgery ablation, but it lacks targeted specificity and causes side effects in normal tissues. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is significantly expressed in TNBC cells, and small interference RNA (siRNA) targeting ROR1 can effectively suppress ROR1 gene expression, thereby inhibiting proliferation and metastasis.
View Article and Find Full Text PDFJ Control Release
December 2024
Department of Chemistry, University of Massachusetts Amherst, 710 North Pleasant Street, Amherst, MA 01003, USA. Electronic address:
Uncontrolled inflammation is the driver of numerous lung diseases. Current treatments, including corticosteroids and bronchodilators, can be effective. However, they often come with notable side effects.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910# Hengshan Road, Shanghai, China.
Assisted reproductive technology (ART) pregnancies present a higher risk of singleton preterm birth than natural pregnancies, but the underlying molecular mechanism remains largely unknown. RNA mA modification is a key epigenetic mechanism regulating cellular function, but the role of mA modification, especially its "reader" YTHDC1, in preterm delivery remains undefined. To delineate the role and epigenetic mechanism of mA modification in ART preterm delivery, the effects of YTHDC1 on trophoblastic function were evaluated by CCK-8, EdU, Transwell, and flow cytometry analyses post its overexpression or knockdown.
View Article and Find Full Text PDFACS Appl Bio Mater
December 2024
Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway, 47500 Subang Jaya, Selangor, Malaysia.
Naked siRNAs are sensitive to enzymatic degradation, phagocytic entrapment, quick renal excretion, membrane impermeability, endosomal escape, and off-target effects. Designing a safe and efficient nanocarrier for siRNA delivery to the target site without toxicity remains a significant hurdle in gene therapy. CA is a unique derivative of hydroxyapatite and a highly pH-sensitive nanocarrier with strong particle aggregation and a high polydispersity index.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
School of Medicine, 411 Hospital of Shanghai University, Shanghai University, Shanghai, 200444, China.
Hepatic diseases cause serious public health problems worldwide, and there is an urgent need to develop effective therapeutic agents. In recent years, significant progress is made in RNA therapy, and RNA molecules, such as mRNAs, siRNAs, miRNAs, and RNA aptamers, are shown to provide significant advantages in the treatment of hepatic diseases. However, the drawbacks of RNAs, such as their poor biological stability, easy degradation by nucleases in vivo, low bioavailability, and low concentrations in target tissues, significantly limit the clinical application of RNA-based drugs.
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