Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft

Jingxin, Xie; Li, Xueyi; Meng, Dan; Liang, Qiujuan; Wang, Xinhong; Wang, Li; Wang, Rui; Xiang, Meng; Chen, SF

doi:10.1016/j.imlet.2016.06.004

Cited by 5 publications

(8 citation statements)

References 38 publications

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“…As in the skin, various groups have administrated IL-10 to kidney disease models via viral gene transfer and in hydrogels. [94][95][96][97] As in colitis, some of the challenges of efficient IL-10 administration have been avoided by using ex vivo modified immune cells, and in so doing also serve as a possible insight into IL-10's complex and interconnected role in the pathophysiology of kidney fibrosis. Indeed, novel therapies for renal fibrosis are not limited to direct application of IL-10 itself: Romero et al reported that l-citrulline, an alphaamino acid, significantly increased IL-10 levels and resulted in remarkably reduced tubulointerstitial fibrosis in a type I diabetic mouse model.…”

Section: Renal Fibrosismentioning

confidence: 99%

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

Steen

Wang

Balaji

et al. 2020

Advances in Wound Care

282

158

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Significance: Fibrosis is the endpoint of chronic disease in multiple organs, including the skin, heart, lungs, intestine, liver, and kidneys. Pathologic accumulation of fibrotic tissue results in a loss of structural integrity and function, with resultant increases in morbidity and mortality. Understanding the pathways governing fibrosis and identifying therapeutic targets within those pathways is necessary to develop novel antifibrotic therapies for fibrotic disease. Recent Advances: Given the connection between inflammation and fibrogenesis, Interleukin-10 (IL-10) has been a focus of potential antifibrotic therapies because of its well-known role as an anti-inflammatory mediator. Despite the apparent dissimilarity of diseases associated with fibrotic progression, pathways involving IL-10 appear to be a conserved molecular theme. More recently, many groups have worked to develop novel delivery tools for recombinant IL-10, such as hydrogels, and cellbased therapies, such as ex vivo activated macrophages, to directly or indirectly modulate IL-10 signaling. Critical Issues: Some efforts in this area, however, have been stymied by IL-10's pleiotropic and sometimes conflicting effects. A deeper, contextual understanding of IL-10 signaling and its interaction with effector cells, particularly immune cells, will be critical to future studies in the field. Future Directions: IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling. The development of novel therapeutics and cell-based therapies that capitalize on targets within the IL-10 signaling pathway could have far-reaching implications for patients suffering from the consequences of organ fibrosis.

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Section: Renal Fibrosismentioning

confidence: 99%

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

Steen

Wang

Balaji

et al. 2020

Advances in Wound Care

282

158

View full text Add to dashboard Cite

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“…Capsid engineering modifies the native AAV capsid to chimeric capsids, mosaic capsids, and transcapsidation via genetically modifying CAP genes ,− and can enable functionalization of AAV for stimuli-responsive gene therapy (Tables and ).…”

Section: Methods Of Aav Engineeringmentioning

confidence: 99%

“…Neutralization by pre-existing nAbs can be avoided, and predetermined tissue tropism can be redirected by cross-packaging AAV DNA from a common serotype into a capsid of another serotype. , To inhibit rejection in a rat kidney transplantation model, AAV2 ITRs were packaged in the AAV1 capsid by co-transfecting producer cells with AAV2 REP and AAV1 CAP genes. ,, Rats received AAV1-IL-10 intramuscularly 8 weeks prior to transplantation, and in another study, intra-arterially the day of transplant. Both methods prevented kidney rejection and avoided neutralization by antibodies. , …”

Section: Methods Of Aav Engineeringmentioning

confidence: 99%

“…AAV is engineered through capsid engineering, surface tethering, and encapsulation in order to address the limitations of native AAV (Figure ). In capsid engineering, the CAP genes are altered to introduce a new peptide or tag (chimeric capsid), two capsids are merged together (mosaic capsid), or an AAV gene construct from one serotype is encapsulated into an alternative capsid serotype (transcapsidation). ,− The AAV surface can be synthetically tethered through conjugation with polymers, ligands, and probes or by complexation with polymers or another type of nano- or microparticle ( e . g ., magnetic microparticles). − AAV can also be encapsulated in larger carriers such as liposomes, extracellular vesicles, or hydrogels to shield them from immune response or blend them into a large-scale biomaterial platform ( e .…”

Section: Challenges and Improvements Of Aav Vectorsmentioning

confidence: 99%

“…The robustness of AAV increases the flexibility of materials handling for production and purification at a desired temperature for multiple days. VP3 protein, making up almost the entirety of the AAV capsid, , can be altered with ease through editing the CAP gene encoding VP3. ,− Intracellular pathways of AAV gene transfer can be molecularly tuned by editing the C AP genes encoding VP1 and VP2, proteins that are exposed and play crucial roles during endosomal processing . The small size (∼25 nm) of AAV is advantageous over other larger viruses as it maximizes the size control in the preparation of larger engineered vectors.…”

Section: Challenges and Improvements Of Aav Vectorsmentioning

confidence: 99%

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Synthetically Engineered Adeno-Associated Virus for Efficient, Safe, and Versatile Gene Therapy Applications

2020

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Gene therapy directly targets mutations causing disease, allowing for a specific treatment at a molecular level. Adeno-associated virus (AAV) has been of increasing interest as a gene delivery vehicle, as AAV vectors are safe, effective, and capable of eliciting a relatively contained immune response. With the recent FDA approval of two AAV drugs for treating rare genetic diseases, AAV vectors are now on the market and are being further explored for other therapies. While showing promise in immune privileged tissue, the use of AAV for systemic delivery is still limited due to the high prevalence of neutralizing antibodies (nAbs). To avoid nAb-mediated inactivation, engineered AAV vectors with modified protein capsids, materials tethered to the capsid surface, or fully encapsulated in a second, larger carrier have been explored. Many of these engineered AAVs have added benefits, including avoided immune response, overcoming the genome size limit, targeted and stimuliresponsive delivery, and multimodal therapy of two or more therapeutic modalities in one platform. Native and engineered AAV vectors have been tested to treat a broad range of diseases, including spinal muscular atrophy, retinal diseases, cancers, and tissue damage. This review will cover the benefits of AAV as a promising gene vector by itself, the progress and advantages of engineered AAV vectors, particularly synthetically engineered ones, and the current state of their clinical translation in therapy.

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Endothelial Cell Isolation and Manipulation

Brostjan

2019

Fundamentals of Vascular Biology

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Transduction of interleukin-10 through renal artery attenuates vascular neointimal proliferation and infiltration of immune cells in rat renal allograft

Cited by 5 publications

References 38 publications

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

Synthetically Engineered Adeno-Associated Virus for Efficient, Safe, and Versatile Gene Therapy Applications

Endothelial Cell Isolation and Manipulation

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