Curing a genetic disease by repairing the underlying genetic defect is a fascinating concept that has been addressed so far by gene compensation therapy. For this, a functional copy of the gene in question together with elements controlling its expression is produced as a vector and introduced ex vivo into the patient's own cells that subsequently are reinfused. Alternatively, vectors are administered directly in vivo. Although this strategy resulted in impressive therapeutic benefits for patients, the ultimate goal of gene therapy, i.e., a cure by repairing the actual genetic or epigenetic defect, remained an unresolved task. With the advent of designer DNA-binding domains, this goal is coming into reach. These domains are either combined with nucleases and used as molecular precision scissors for introducing DNA breaks at defined sites in the cell's genome preparing for position-selective DNA repair, or they are used as programmable DNA-binding units for positioning epigenome-modifying domains to predefined target sequences. However, for reaching its full potential, these components need to be delivered into cells in an efficient and safe manner. Here, we summarize current viral and non-viral delivery approaches applicable for genome and epigenome editing and discuss their respective advantages and limitations.
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http://dx.doi.org/10.1007/978-1-4939-7774-1_7 | DOI Listing |
Discov Oncol
January 2025
Department of Biotechnology, School of Bio Sciences and Technology (SBST), Vellore Institute of Technology (VIT), Vellore, 632014, India.
Cancer, one of the deadliest diseases, has remained the epicenter of biological research for more than seven decades. Yet all the efforts for a perfect therapeutic cure come with certain limitations. The use of medicinal plants and their phytochemicals as therapeutics has received much attention in recent years.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Chemical Engineering, University of Massachusetts Amherst, Amherst, Massachusetts 01003, United States.
The innate immune system is tightly regulated by a complex network of chemical signals triggered by pathogens, cellular damage, and environmental stimuli. While it is well-established that changes in the extracellular environment can significantly influence the immune response to pathogens and damage-associated molecules, there remains a limited understanding of how changes in environmental stimuli specifically impact the activation of the NLRP3 inflammasome, a key component of innate immunity. Here, we demonstrated how shear stress can act as Signal 2 in the NLRP3 inflammasome activation pathway by treating LPS-primed immortalized bone marrow-derived macrophages (iBMDMs) with several physiologically relevant magnitudes of shear stress to induce inflammasome activation.
View Article and Find Full Text PDFBiomater Sci
January 2025
Department of Urology, The Third Xiangya Hospital of Central South University, No. 138, Tongzipo Road, Changsha, 410013, Hunan, China.
Gemcitabine (GEM) is a first line chemotherapy drug for bladder cancer (BCa). GEM's lack of specificity has led to disadvantages, resulting in low efficiency, especially when combined with the targeted treatment of BCa stem cells (CSCs), which is considered the cause of BCa recurrence and progression. To enhance the anti-cancer effect and reduce the side effects of GEM targeting of BCa cells/CSCs, an aptamer drug conjugate (ApDC) targeted delivery system was used to improve the efficiency of GEM in BCa therapy using EpCAM aptamer-GEM conjugates based on the epithelial cell adhesion molecule (EpCAM), which is highly expressed on the cell membrane of BCa cells/CSCs.
View Article and Find Full Text PDFJ Phys Ther Educ
January 2025
Megan H. Ross is the postdoctoral research fellow at the The University of Queensland, Brisbane 4072, Australia Please address all correspondence to Megan H. Ross.
Introduction: The objective of this study is to develop and evaluate an evidence-based, clinically relevant, and user-friendly eLearning resource to facilitate the provision of safe and affirming physical therapy services for individuals with lesbian, gay, bisexual, transgender, queer, intersex, and other related identities or experiences (LGBTQIA+).
Review Of Literature: When accessing physical therapy, individuals who are LGBTQIA+ can experience assumptions, discrimination, discomfort, and encounter health professionals who lack knowledge about LGBTQIA+ health.
Subjects: Nine consumers and end-users participated in codesign and 20 physical therapists (evaluated the resource).
Curr Gene Ther
January 2025
Department of Pharmacology, Faculty of Medicine, The University of Jordan, Queen Rania Al-Abdullah Street, Amman 11942, Jordan.
Introduction: Liposomes are versatile delivery systems for encapsulating small interfering RNAs (siRNAs) because they enhance cellular uptake and gene silencing. This study compares the new liposome formula to commercial lipofectamine in delivering siRNAs targeting hepatic carcinoma genes, focusing on HNF4-α and PFKFB4.
Methods: Flow cytometry and confocal microscopy revealed efficient internalization of PE-Rhod- B labeled lipoplexes in HepG2 cells, while cytotoxicity assays demonstrated significant reductions in cell viability, particularly with siHNF4-α and siPFKFB4.
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