Gene Therapy
Danilo D. Lasic in LIPOSOMES in GENE DELIVERY, 2019
At present, gene therapy approaches are targeted toward somatic cells, i.e., they would affect only nonreproductive cells. Germ cell therapy, involving transfection of ova and sperm cells, however, brings about, in addition to scientific problems, a variety of ethical, social, and philosophical issues which will have to be solved before we may continue with applications of this research. Therefore, in vivo gene therapy, as a logical development of ex vivo treatments (i.e., direct injection instead of collection of some cells, transfection in the test tube, and reinjection), envisages targeting of tissues or cells of certain organs, such as heart, lung, blood, vascular endothelium, liver (hepatocytes or macrophages), spleen, lymph nodes, muscle, pancreas and other glands, muscle (fibroblasts), potentially brain and nerve cells, skin, thymus, and others upon systemic or local application. Among hundreds of different cells in various tissues, macrophages and monocytes, vascular endothelium, hepatocytes, lung epithelium, neural muscle, stem and mucosal cells, and adipocytes seem to be the primary targets.
Epidermal Keratins
John P. Sundberg in Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
To date, transgenic studies have shown that reverse genetic experiments can be powerful tools to study keratin function and have prompted investigations that have led to the discovery of the molecular basis for two dominantly inherited skin diseases, EBS and EHK. We have also exploited the expression characteristics of various epidermal genes to target exogenous gene expression exclusively to the epidermis and hair follicle. In this way, we have observed the effects of overexpression of growth factors, such as TGFα44 and TGFβ,45 and protooncogenes, such as v-ras46 and v-fos.47 These mice exhibit profound epidermal changes and have provided us with the means to identify the contribution of each of these proteins to normal skin function and to the disease state. Moreover, these mice will allow us to assess the viability of somatic gene therapy approaches for the amelioration of human skin diseases. Somatic gene therapy is expected to provide new therapies for many diseases that have been recalcitrant to conventional pharmacological or surgical therapy,48 and given its accessibility and ease of handling, the skin will be an important site of entry for these new technologies.
Connecting lines from an ethical point of view
Elisabeth Hildt, Dietmar Mieth in In Vitro Fertilisation in the 1990s, 2018
Clearly, PID and human gene therapy make us aware of our responsibility to future generations. But it remains difficult to clarify how is to be integrateted the well-being of future generations. I must therefore stress once again the need for a careful risk assessment, in agreement with the Report on the Ethical Implications of Biotechnoloy, by the Group of Advisors to the European Commission (1996, p.17): Because of its present risk assessment, somatic gene therapy should be restricted to serious diseases for which there is no other effective available treatment… Because of the important controversial and unprecedented questions raised by germ-line therapy, and considering the actual state of die art, germline gene therapy on humans is not at the present time ethically acceptable.
From pathogenesis to novel therapies in primary hyperoxaluria
Published in Expert Opinion on Orphan Drugs, 2019
Gill Rumsby, Sally-Anne Hulton
There are currently no published studies using CRISPR/Cas9 gene editing as a means of correcting the mutations causing PH but, as single gene disorders, they are potentially suitable for this approach. In addition, by the introduction of mutations, the technique could be used to knockout GO and LDHA genes to allow modification of oxalate production. A recent publication has in fact described this approach to inhibit GO activity in a mouse model of PH1 and showed a reduction in GO enzyme expression and urine oxalate excretion [92]. Somatic cell treatment will, however, come up against the same problems seen with gene therapy, namely access to the appropriate tissue and the need for the edited cells to be incorporated and predominate to overcome oxalate production in the remainder of the native cells. Germline gene editing with this technique has been used in animals for other disorders but has much wider ethical implications for human use as changes will be heritable and, at the present time, there is a moratorium on such experiments [93]. It will also not offer a cure for those who already have the disease. Where CRISPR/Cas9 may play an earlier role is in the production of humanized transplantable organs in pigs, increasing the availability of transplants with lowered immunogenic potential allowing reduction of immunosuppressive therapy [94–96].
Gene and cell therapy and nanomedicine for the treatment of multiple sclerosis: bibliometric analysis and systematic review of clinical outcomes
Published in Expert Review of Neurotherapeutics, 2021
Javier Caballero-Villarraso, Jamil Sawas, Begoña M. Escribano, Francisco A. Martín-Hersog, Andrea Valverde-Martínez, Isaac Túnez
Gene therapy could be defined as the set of techniques that allow the conveyance of DNA or RNA sequences inside target cells, in order to modulate the expression of certain genes that are altered, thus reversing the biological disorder previously induced [13,14]. Depending on the type of target cell, there are two modalities of gene therapy: germ cell gene therapy and somatic gene therapy. Furthermore, depending on the applied strategy, it can also be classified into in vivo and ex vivo gene therapy. To achieve a certain biological effect in gene therapy, it is necessary to efficiently transfer (introduce) the gene sequence of interest into the target cell and subsequently obtain its expression pattern in the host cell. Physico-chemical gene transfer methods include: microinjection, calcium phosphate precipitation, electroporation, microprojectile bombardment, direct injection of ‘naked’ DNA, DNA-protein conjugates, DNA-adenovirus conjugates, and liposomes [13–15].
Perceptions of airway gene therapy for cystic fibrosis
Published in Expert Opinion on Biological Therapy, 2023
Martin Donnelley, David Parsons, Ivanka Prichard
To date, only two studies have specifically examined perceptions of gene therapy for CF. In 2003 Iredale et al. performed a qualitative pilot study to examine the attitudes of people with CF and members of the public [16]. They found support for somatic gene therapy, and hesitancy about germline gene therapy, as well as opposition to gene therapy for enhancement purposes. In 2006 Jaffe et al. performed a short seven question single-center quantitative study that examined parental attitudes toward gene therapy for children with CF in the UK [15]. They found that parents of children with CF reported that gene therapy was an important part of CF research, however safety was still considered a major issue, especially when considering gene therapy for children. While important, these two studies only provide information on the opinions of small populations (N = 22 and N = 80, respectively) from 15+ years ago, well before gene therapies had experienced success across a range of other diseases.
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