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Nanomedicine Against COVID-19
Published in Hanadi Talal Ahmedah, Muhammad Riaz, Sagheer Ahmed, Marius Alexandru Moga, The Covid-19 Pandemic, 2023
Saima Zulfiqar, Zunaira Naeem, Shahzad Sharif, Ayoub Rashid Ch., M. Zia-Ul-Haq, Marius Moga
Naked DNA just like mRNA can also be degraded by nucleases leading to their incomplete delivery and immune response. Nanocarriers based on synthetic/ natural polymers, inorganic particles, and cationic lipids are the most suitable for formulation of DNA containing vaccines. Polymeric nanoparticles with encapsulation of DNA can avoid its biological degradation resulting in controlled and targeted release of drug [155, 156]. For the specific antigen-antibody response PLGA nanotransporters are the extensively researched for the development of DNA based vaccines. They can improve the DNA loading and release with the prevention against degradation in biological system. These PLGA nanoparticles can be synthesized as: Cationic glycol-chitosan and PLGA;Polyethylenimine and PLGA [157, 158].
A Short Introduction to DNA Methylation
Published in Cristina Camprubí, Joan Blanco, Epigenetics and Assisted Reproduction, 2018
Transcription does not occur on naked DNA but in the context of chromatin, which critically influences the accessibility of the DNA to transcription factors and the DNA polymerase complexes. DNA methylation, histone modifications and chromatin remodeling are closely linked and constitute multiple layers of epigenetic modifications to control and modulate gene expression through chromatin structure. DNMTs and histone deacetylases (HDACs) are found in the same multi-protein complexes and methyl CpG-binding domain proteins (MBDs) interact with HDACs, histone methyltransferases as well as with the chromatin remodeling complexes. Furthermore, mutations or loss of members of the SNF2 helicase/ATPase family of chromatin remodeling proteins such as ATRX or LSH lead to genome-wide perturbations of DNA methylation patterns and inappropriate gene expression programs.
Gene Therapy
Published in John C Watkinson, Raymond W Clarke, Louise Jayne Clark, Adam J Donne, R James A England, Hisham M Mehanna, Gerald William McGarry, Sean Carrie, Basic Sciences Endocrine Surgery Rhinology, 2018
Seiji B. Shibata, Scott M. Graham
Naked DNA is one of the most extensively studied methods of gene therapy. This non-viral method of gene therapy has several advantages. These include simplicity, ease of large scale production, minimal immune response and safety.26 The major obstacle for plasmid gene therapy is efficiency. When DNA is placed in an organism, most of the DNA is not internalized. Even if internalization does occur, endosomal degradation destroys nearly all of the remaining plasmid prior to nuclear membrane transit and expression of the desired gene does not occur. In addition, since plasmid uptake is not receptor-mediated, targeting of the plasmid to a specific cell also remains a major obstacle. In the past 25 years, substantial progress has been made in overcoming these obstacles to non-viral gene transfer. Lastly, plasmid-mediated transfer results in transient expression because the plasmid is lost with cell division. Several methods using site-specific integration or expression of viral proteins have shown promise as a means to overcome this difficulty.27, 28 Many of the past therapeutic attempts to utilize plasmid-mediated gene transfer have shown only modest potential. However, as all aspects of plasmid efficiency increase, this should directly correlate with the ability to utilize this technology in therapeutic interventions.
Gene therapy to terminate tachyarrhythmias
Published in Expert Review of Cardiovascular Therapy, 2022
Kohei Kawajiri, Kensuke Ihara, Tetsuo Sasano
Naked DNA plasmid is a simple and safe non-viral gene delivery system. In this method, naked DNA plasmid is injected into the target area via direct or intracoronary injection [14,15]. Immune reactions are a side effect when using virus vectors, but the advantage of naked DNA plasmids is that there are fewer antibody-mediated immune responses, and it is relatively easy to produce vectors. The disadvantage of selecting naked DNA plasmids is the very low transduction rate [16]. Expression levels and duration after the injection of naked DNA are generally limited because naked plasmids are rapidly degraded by nucleases and the mononuclear phagocyte system [17]. Therefore, viral vectors may be suitable for congenital and acquired arrhythmias that require long-term and diffuse treatment. STOP-HF (Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure) is a clinical trial utilizing plasmid DNA in humans [18]. Endomyocardial injection of plasmid harboring CXCL12 gene which codes stromal cell-derived factor-1 (SDF-1) in patients with ischemic heart failure was shown to be safe and to improve LV remodeling and decrease the level of N-terminal pro-B-type natriuretic peptides.
Developing models of cholangiocarcinoma to close the translational gap in cancer research
Published in Expert Opinion on Investigational Drugs, 2021
Scott H. Waddell, Luke Boulter
Modeling CCA with hydrodynamic tail vein injections generates tumors quickly while under an intact immune surveillance (Figure 4, top panel). Additionally, the researcher can define the genetic landscape of tumors (to some extent). One major limitation of the hydrodynamic tail vein model is that all tumors are derived from hepatocytes, and as such, this tool is wrapped in the debate discussing cell-of-origin of CCA as mentioned above. To generate CCA from hepatocytes, the hydrodynamic tail vein model must include one DNA plasmid that drives hepatocyte-to-cholangiocyte transdifferentiation, and this therefore shapes the molecular profile of the resulting CCA tumors. However, other oncogenes of interest and reporter genes can easily be integrated to form a cocktail of naked DNA for injection. This method thus allows assessment of the contribution individual genes make to tumor initiation, development, shaping the tumor microenvironment (TME) and responding to therapeutics. The amenability of the hydrodynamic tail-vein injection model in combination with in vivo therapeutic experiments makes it a valuable tool to study genomic-drug interactions.
Novel polyethyleneimine-R8-heparin nanogel for high-efficiency gene delivery in vitro and in vivo
Published in Drug Delivery, 2018
Linjiang Song, Xiuqi Liang, Suleixin Yang, Ning Wang, Tao He, Yan Wang, Lan Zhang, Qinjie Wu, Changyang Gong
Increasing attention has been focused on gene therapy, because it provides a promising approach to treat many diseases including cancers by delivering genetic drugs into target cells and tissues (Yang et al., 2007; Wang et al., 2012). Naked DNA is unsuitable for in vivo application, as it is easily degraded by serum nucleases and rapidly eliminated by renal excretion (Bumcrot et al., 2006; Kim et al., 2016). Therefore, a suitable gene delivery system that could protect nucleic acid from degradation and selectively deliver them into target cells is needed. Even though the viral vectors exhibited high transfection efficiency, it is limited to further application in clinic because of the inherent immunogenicity, insertional mutagenesis and possibly carcinogenicity (Lehrman, 1999; Kay et al., 2001). Recently, nonviral vectors have attracted more attention in gene therapy. Nonviral vectors, such as cationic polymers, dendrimers, lipids and peptides, are characterized by low immunogenicity and facile fabrication and thus used as promising gene delivery system (Elsabahy et al., 2011; Yin et al., 2014; Jeong et al., 2016).