Site-Specific PEGylated Adeno-Associated Viruses with Increased Serum Stability and Reduced Immunogenicity

Yao, Tianzhuo; Zhou, Xueying; Zhang, Chuanling; Yu, Xintong; Tian, Zhen‐Yu; Zhang, Lihe; Zhou, Demin

doi:10.3390/molecules22071155

Cited by 41 publications

(42 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although there both our method and the commercial kit resulted in the same reduction in infectivity, we are confident that we will be able to improve our method further by reducing the effect of NAEK incorporation. Based on our recently published data, mutants at sites Q325, Q325+1, S452, S452+1, G453, G453+1 E458, E548+1, and S662 exhibited a 1.0–2.0‐fold increase in viral infectivity compared to that of wild‐type AAV‐2 . As this study served as a proof of concept, we are currently studying these new sites, which may be more suitable for fluorescent labeling.…”

Section: Discussionmentioning

confidence: 68%

Precision Fluorescent Labeling of an Adeno‐Associated Virus Vector to Monitor the Viral Infection Pathway

Zhang

Zhou

Yao

et al. 2018

Biotechnology Journal

Self Cite

View full text Add to dashboard Cite

Adeno-associated virus 2 (AAV2) is a common vehicle for the delivery of a variety of therapeutic genes. A better understanding of the process of infection of AAV2 will advance our knowledge of AAV2 biology and allow for the optimization of AAV2 capsids with favorable transduction profiles. However, the precise fluorescent labeling of an AAV2 vector for probing virus tracking without affecting the nature of the virus remains a challenge. In this study, a lab-synthesized azide-moieties on the viral capsid at modifiable sites is precisely displayed. Upon bioorthogonal copper-less click reaction, fluorophores are subsequently conjugated to AAV2 vectors for visualization of particles. Using this principle, the authors demonstrate that it can be used for visibly studying the cell entry, and intracellular trafficking of AAV2 particles, enabling the monitoring of the intracellular dynamics of AAV2 infection. This study provides new insights into the precision labeling of AAV2 particles with important implications for a better understanding of the molecular mechanism of therapeutic gene delivery.

show abstract

Section: Discussionmentioning

confidence: 68%

Precision Fluorescent Labeling of an Adeno‐Associated Virus Vector to Monitor the Viral Infection Pathway

Zhang

Zhou

Yao

et al. 2018

Biotechnology Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…For the latter point, to circumvent Ab-mediated neutralization that could limit their efficacy, owing to the >70% AAV serotype 2 seropositivity of the population and notably T-cell mediated responses, AAV vector particles are often injected into muscles [35]. Interestingly, association of AAV vectors to extracellular vesicles or vector pegylation were shown to induce escape from neutralizing antibodies and represents an attractive gene delivery option [36][37][38].…”

Section: General Notions Of Vector Designmentioning

confidence: 99%

Towards Physiologically and Tightly Regulated Vectored Antibody Therapies

Page

Fusil

Cosset

2020

Cancers

View full text Add to dashboard Cite

Cancers represent highly significant health issues and the options for their treatment are often not efficient to cure the disease. Immunotherapy strategies have been developed to modulate the patient’s immune system in order to eradicate cancerous cells. For instance, passive immunization consists in the administration at high doses of exogenously produced monoclonal antibodies directed either against tumor antigen or against immune checkpoint inhibitors. Its main advantage is that it provides immediate immunity, though during a relatively short period, which consequently requires frequent injections. To circumvent this limitation, several approaches, reviewed here, have emerged to induce in vivo antibody secretion at physiological doses. Gene delivery vectors, such as adenoviral vectors or adeno-associated vectors, have been designed to induce antibody secretion in vivo after in situ cell modification, and have driven significant improvements in several cancer models. However, anti-idiotypic antibodies and escape mutants have been detected, probably because of both the continuous expression of antibodies and their expression by unspecialized cell types. To overcome these hurdles, adoptive transfer of genetically modified B cells that secrete antibodies either constitutively or in a regulated manner have been developed by ex vivo transgene insertion with viral vectors. Recently, with the emergence of gene editing technologies, the endogenous B cell receptor loci of B cells have been modified with the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas-9) system to change their specificity in order to target a given antigen. The expression of the modified BCR gene hence follows the endogenous regulation mechanisms, which may prevent or at least reduce side effects. Although these approaches seem promising for cancer treatments, major questions, such as the persistence and the re-activation potential of these engineered cells, remain to be addressed in clinically relevant animal models before translation to humans.

show abstract

“…Young课题组 [61] [63] . 因此, Young和Cao 课题组 [64,65] 利用基因密码子扩展技术实现了对CAR-T 活化过程的调控(switchable CAR-T, sCAR-T)(图2 AAV在血清中的稳定性提高了约两倍 [67] . 另一方面, 为增强AAV的靶向性, Zhou [68] 和Chatterjee课题组 [69] 分别成功利用基因密码子扩展技术和正交化策略将靶向整合素的环肽cRGD位点特异性地连接到AAV的衣壳蛋白上, 使该病毒选择性地靶向高表达整合素的细胞, 显著提高了疗效.…”

Section: 通过合适的连接臂抗体也可直接与癌细胞受体unclassified

“…[72] . 后来, Zhou课题组 [73] 扰素-α2b (IFN-α2b) [74] 、成纤维细胞生长因子21 (fibroblast growth factor 21, FGF21) [75] 、白介素-4 (interleukin-4, IL-4) [76] 以及AAV [67] 等.…”

Section: 通过合适的连接臂抗体也可直接与癌细胞受体mentioning

confidence: 99%