Non-viral Gene Therapy for Osteoarthritis

Uzielienè, Ilona; Kalvaityte, Ursule; Bernotienė, Eiva; Mobasheri, Ali

doi:10.3389/fbioe.2020.618399

Cited by 29 publications

(38 citation statements)

References 77 publications

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“…For example, in adjuvant arthritis mice models for RA, IL-10 inducers or IL-10 producing cells (e.g., Th2, Tregs) attenuated clinical phenotypes and normalized IL-10 levels after 28 days of administration (Lutsenko et al, 2014). In another pro-inflammatory disorder, osteoarthritis, increased IL-10 expression significantly decreased pain in a dog model, supporting the benefits of IL-10 prophylactics for inflammatory conditions (Uzieliene et al, 2021). IL-10 also prevents PAH via suppressed antigen presentation by macrophages and DCs, blunted proinflammatory cytokine release, and activated Treg cells (Lai et al (2011); Jafri and Ormiston, 2017).…”

Section: Il-10 Administration and Inductionmentioning

confidence: 88%

Manipulating CD4+ T Cell Pathways to Prevent Preeclampsia

Murray

Gumusoglu

Santillan

et al. 2022

Front. Bioeng. Biotechnol.

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Preeclampsia (PreE) is a placental disorder characterized by hypertension (HTN), proteinuria, and oxidative stress. Individuals with PreE and their children are at an increased risk of serious short- and long-term complications, such as cardiovascular disease, end-organ failure, HTN, neurodevelopmental disorders, and more. Currently, delivery is the only cure for PreE, which remains a leading cause of morbidity and mortality among pregnant individuals and neonates. There is evidence that an imbalance favoring a pro-inflammatory CD4+ T cell milieu is associated with the inadequate spiral artery remodeling and subsequent oxidative stress that prime PreE’s clinical symptoms. Immunomodulatory therapies targeting CD4+ T cell mechanisms have been investigated for other immune-mediated inflammatory diseases, and the application of these prevention tactics to PreE is promising, as we review here. These immunomodulatory therapies may, among other things, decrease tumor necrosis factor alpha (TNF-α), cytolytic natural killer cells, reduce pro-inflammatory cytokine production [e.g. interleukin (IL)-17 and IL-6], stimulate regulatory T cells (Tregs), inhibit type 1 and 17 T helper cells, prevent inappropriate dendritic cell maturation, and induce anti-inflammatory cytokine action [e.g. IL-10, Interferon gamma (IFN-γ)]. We review therapies including neutralizing monoclonal antibodies against TNF-α, IL-17, IL-6, and CD28; statins; 17-hydroxyprogesterone caproate, a synthetic hormone; adoptive exogenous Treg therapy; and endothelin-1 pathway inhibitors. Rebalancing the maternal inflammatory milieu may allow for proper spiral artery invasion, placentation, and maternal tolerance of foreign fetal/paternal antigens, thereby combatting early PreE pathogenesis.

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Section: Il-10 Administration and Inductionmentioning

confidence: 88%

Manipulating CD4+ T Cell Pathways to Prevent Preeclampsia

Murray

Gumusoglu

Santillan

et al. 2022

Front. Bioeng. Biotechnol.

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“…The transgene is inserted into the plasmid directly followed by delivery into the cells. Non-viral gene delivery systems can be categorized into physical methods such as electroporation, sonoporation, photoporation, hydroporation, and magnetofection or chemical carriers such as inorganic particles and synthetic/biodegradables ( 139 , 140 ). Compared to viral vectors, plasmids are relatively safe as there is no risk of integrating with the host genome which also allows for potential re-dosing with low immunogenicity.…”

Section: Ex Vivo Gene Therapymentioning

confidence: 99%

Gene therapy approaches for equine osteoarthritis

Thampi

Samulski²,

Grieger³

et al. 2022

Front. Vet. Sci.

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With an intrinsically low ability for self-repair, articular cartilage injuries often progress to cartilage loss and joint degeneration resulting in osteoarthritis (OA). Osteoarthritis and the associated articular cartilage changes can be debilitating, resulting in lameness and functional disability both in human and equine patients. While articular cartilage damage plays a central role in the pathogenesis of OA, the contribution of other joint tissues to the pathogenesis of OA has increasingly been recognized thus prompting a whole organ approach for therapeutic strategies. Gene therapy methods have generated significant interest in OA therapy in recent years. These utilize viral or non-viral vectors to deliver therapeutic molecules directly into the joint space with the goal of reprogramming the cells' machinery to secrete high levels of the target protein at the site of injection. Several viral vector-based approaches have demonstrated successful gene transfer with persistent therapeutic levels of transgene expression in the equine joint. As an experimental model, horses represent the pathology of human OA more accurately compared to other animal models. The anatomical and biomechanical similarities between equine and human joints also allow for the use of similar imaging and diagnostic methods as used in humans. In addition, horses experience naturally occurring OA and undergo similar therapies as human patients and, therefore, are a clinically relevant patient population. Thus, further studies utilizing this equine model would not only help advance the field of human OA therapy but also benefit the clinical equine patients with naturally occurring joint disease. In this review, we discuss the advancements in gene therapeutic approaches for the treatment of OA with the horse as a relevant patient population as well as an effective and commonly utilized species as a translational model.

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“…As an alternative to controversial viruses, non-viral gene therapy drug delivery has the potential to tackle many of the limitations of viral vectors, particularly with respect to safety, the ability to deliver larger genetic payloads and the simplicity of synthesis, as compared to viral counterparts [34,35]. One of the most important particularities of non-viral vectors is the protection of carried gene therapy drugs against premature degradation in physiological fluids and extracellular space before reaching the site of action, which represents the driving factor in improving circulation time, intracellular transfection efficiency and therapeutic outcomes, respectively [36]. The main strengths, challenges and opportunities of viral and non-viral vectors in gene therapy drug delivery are presented in Table 1.…”

Section: Non-viral Vector Gene Therapy Drug Delivery Platformmentioning

confidence: 99%

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

2022

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Gene-based therapy represents the latest advancement in medical biotechnology. The principle behind this innovative approach is to introduce genetic material into specific cells and tissues to stimulate or inhibit key signaling pathways. Although enormous progress has been achieved in the field of gene-based therapy, challenges connected to some physiological impediments (e.g., low stability or the inability to pass the cell membrane and to transport to the desired intracellular compartments) still obstruct the exploitation of its full potential in clinical practices. The integration of gene delivery technologies with electrospun fibrous architectures represents a potent strategy that may tackle the problems of stability and local gene delivery, being capable to promote a controlled and proficient release and expression of therapeutic genes in the targeted cells, improving the therapeutic outcomes. This review aims to outline the impact of electrospun-fibrous-architecture-mediated gene therapy drug delivery, and it emphatically discusses the latest advancements in their formulation and the therapeutic outcomes of these systems in different fields of regenerative medicine, along with the main challenges faced towards the translation of promising academic results into tangible products with clinical application.

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Non-viral Gene Therapy for Osteoarthritis

Cited by 29 publications

References 77 publications

Manipulating CD4+ T Cell Pathways to Prevent Preeclampsia

Manipulating CD4+ T Cell Pathways to Prevent Preeclampsia

Gene therapy approaches for equine osteoarthritis

Electrospun-Fibrous-Architecture-Mediated Non-Viral Gene Therapy Drug Delivery in Regenerative Medicine

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