China
Africa
Explore chapters and articles related to this topic
Unilateral Ex Vivo Gene Therapy by GDNF in Neurodegenerative Diseases
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Sonia Barua, Yashwant V. Pathak
In the ex vivo technique, cells are harvested outside of the patient’s body and used in the viral transduction in the ex vivo laboratory setting. The transduced cells are then injected back into the patient to deliver the therapeutic genes. On the other hand, with the in vivo method, virus loading with therapeutic genes is directly injected into the patient. Commonly used viral vectors are adenovirus, adeno-associated virus (AAV), lentivirus and retrovirus for both ex vivo and in vivo gene therapy. AAV is considered an ideal vector in gene therapy due to its unique properties. More importantly, it reduces the risk of immune response by containing no viral genes. In addition, AAV provides long-term gene expression. This vector is mostly employed in in vivo gene delivery due to its long-term gene expression, which limits the number of treatment administrations. However, the drawback of AAV is its low carrying capacity—approximately 4.5 kb per particle as compared to other vectors. The major drawbacks of in vivo techniques include low survival rates of grafted cells; it can cause migration and proliferation, in particular for stem-cell lines; immunosuppression may be needed; and the preparation of cells is a time-consuming and complex process. Thus, ex vivo has been considered as a potential gene therapy that overcomes the challenges of in vivo methods.
Optogenetic Modulation of Neural Circuits
Published in Francesco S. Pavone, Shy Shoham, Handbook of Neurophotonics, 2020
Mathias Mahn, Oded Klavir, Ofer Yizhar
To circumvent some of the drawbacks of brain-wide expression of optogenetic tools, a more localized approach involves the use of viral vectors for region-specific gene targeting. This approach benefits from localized expression patterns of viral vectors and is more versatile and cost-effective compared with the transgenic approach. Viral vectors are engineered viruses, genetically modified to remove pathogenic gene sequences and, most typically, prevent additional replication and transduction cycles that are part of the natural life-cycle of wild-type viruses (Verma and Weitzman, 2005). Viral vectors used for optogenetic experiments are typically derived from the adeno-associated virus (AAV) and lentivirus (LV) families. AAV-based vectors are the most commonly used, as they are less immunogenic, thereby minimizing immune activation upon injection into brain tissue, and since they do not broadly integrate into the host genome but rather remain inside the nucleus as episomes (Duan et al., 1998). Despite the limited payload size of viral vectors (Grieger and Samulski, 2005, for AAV), some minimal promoter fragments can be used that retain cell-type specificity (Yizhar et al., 2011b). In such cases, the viral vector can be used in non-transgenic animals and achieve specific expression, e.g. in cortical excitatory neurons (CaMKII, Dittgen et al., 2004), hypothalamic hypocretin-secreting neurons (Adamantidis et al., 2007), oxytocinergic neurons (Knobloch et al., 2012), or astrocytes (Jakobsson et al., 2003; Gradinaru et al., 2009).
Emerging Pulmonary Delivery Strategies in Gene Therapy: State of the Art and Future Considerations
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Gabriella Costabile, Olivia M. Merkel
A virus is a biological entity that can penetrate into the cell nucleus of the host and exploit the cellular machinery to express its own genetic material and replace it, then spread to other cells. Viral vectors refer to the use of viruses to deliver genetic materials to the cell. They are extremely attractive because of their ability to enter the cells and their nucleus, but also to induce high transduction efficiency and, depending on the type of viruses employed, e.g. retroviruses, provide also transient or long-term gene expression which is currently difficult to accomplish with non-viral methods (Ibraheem et al. 2014). Several kinds of modified “non-aggressive” viruses have been studied to be used as potential vectors Table 15.1.
Safe and efficient DNA delivery based on tannic acid-ion coordination encapsulation
Published in Soft Materials, 2023
Liang Liu, Chaobing Liu, Zhaojun Yang, Yiran Chen, Shuheng Wu, Xin Chen
Gene therapy is a therapeutic strategy that has shown great promise in the treatment of genetic diseases and tumors.[1–3] However, how to safely and efficiently deliver genes to target cells is still one of the bottlenecks restricting their development. As a kind of vector that has been studied and applied earlier, viral gene vector has the advantages of high transfection efficiency and good biocompatibility, and it is still the main force in the clinical application of gene therapy.[4,5] For example, lentivirus and adenovirus have played an important role in clinical gene therapy in the past and now.[6,7] Unfortunately, with the deepening of research and the development of clinical applications, it is found that these viral vectors showed side effects that cannot be incorporated, such as immunogenicity and tumorigenicity.[8–10] In view of this, with the continuous development of material science, a variety of organic and inorganic materials have been studied and confirmed to have the ability of gene delivery.[11] Materials, such as cationic liposomes,[12] organic and inorganic nanoparticles,[13] cationic polymers,[14,15] and natural polysaccharides,[16,17] can condense DNA by electrostatic or other effects, and deliver it into cells, which can be efficiently expressed. These advances in research on so-called non-viral gene vectors have once again brought light to the further development of gene therapy.[18,19]
Nonviral gene delivery using PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from human papillomavirus type 11 E2 protein
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Jeil Lee, Yong-Eun Kwon, Jaegi Kim, Dong Woon Kim, Hwanuk Guim, Jehyeong Yeon, Jin-Cheol Kim, Joon Sig Choi
Gene therapy is an advanced method of genetic modification, allowing the revision and editing of abnormal genes and suppression of unwanted genes for the treatment of diseases [1]. Generally, vectors, the gene carriers used for gene therapy, are of two types, viral and nonviral. Viral vectors are used in the treatment of diseases and have been developed as gene medicines owing to their excellent transduction and infection capacity in host cells. Viral vectors are used in the treatment of diseases and have been developed as therapeutics owing to their excellent transduction and infection capacity in host cells. Viral vectors have some problems, notably high immunogenicity, recoverability of pathogenicity, induction of point mutations, and high treatment costs, despite their excellent efficiency [2].
Enhanced transfection efficiency of low generation PAMAM dendrimer conjugated with the nuclear localization signal peptide derived from herpesviridae
Published in Journal of Biomaterials Science, Polymer Edition, 2021
Jeil Lee, Yong-Eun Kwon, Younjin Kim, Joon Sig Choi
Viral vectors have been widely investigated as carriers to treat diseases due to high transfection and infection efficiency in host cells. Considering that all existing gene medicines and most candidates being tested in clinical trials are viral vectors, viruses may be optimized carriers for gene therapy [4, 5]. Despite these advantages, problems with viral vectors remain: renewability as pathogenic wild type, carcinogenesis by insertion mutation, excessive immune response, and enormous production and dosing costs. Many researchers have shifted attention to nonviral vectors as alternatives to the safety concern and economic problems associated with viral vectors.