On your MARCKS, get set, deliver: Engineering extracellular vesicles.
On your MARCKS, get set, deliver: Engineering extracellular vesicles.
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在您的 MARCKS 上，准备好，交付：工程细胞外囊泡。
DOI：
10.1016/j.ymthe.2021.04.013
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Witwer,KennethW
中科院分区：
文献类型：
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作者：
Witwer,KennethW
胞外囊泡(EV)作为药物输送平台，在某些情况下优于合成纳米颗粒。1 EVS包括脂质双层封闭的细胞质内容物，并自然包括膜结合蛋白，其中一些已用于工程和货物装载。由于这些蛋白质中的一些受到细胞表达和低EV密度的限制，Dooley等人说。2(在本期《分子治疗》杂志上)Codiak BioSciences严谨地寻找在电动汽车中高度表达和丰富的膜相关蛋白，因此非常适合电动汽车工程中的新应用。他们确定了EWI免疫球蛋白和Marcks家族的成员，这些成员似乎是非常通用的“支架”，用于装载从细胞因子到Cas9再到抗原的各种货物。此外，他们还对稳定性最好的候选药物进行生物工程，并在体内进行测试。2自从电动汽车研究首次合并为一个领域以来，电动汽车的交付潜力已经被认识到。电动汽车工程的原型在2005年由Rose Johnstone组织的第一届电动汽车生物学国际会议上提出。Delcayre等人的目标是“有针对性地将带有新配体或抗体的囊泡输送到特定组织”。3例Anosys表达的可溶性蛋白与乳胶粘附素的C1C2结构域(MFGE8)融合。乳胶粘附素在某些细胞中运输到内小体，并被结合到多囊体内的EVS中，释放时被称为“外小体”(与质膜来源的“外小体”相反)。这种“外切体展示”技术被用来装饰带有HIV-1Nef蛋白、白介素2(IL-2)和粒/单核细胞集落刺激因子(GM-CSF)的EV，保留了生物活性并有机会引发免疫反应。
Extracellular vesicles (EVs) serve as drug delivery platforms that are, in some cases, superior to synthetic nanoparticles. 1 EVs comprise lipid bilayer-enclosed cytoplasmic content and naturally include membraneassociated proteins, several of which have been used for engineering and cargo loading. Since some of these proteins are limited by meager cellular expression and low EV density, Dooley et al. 2 (in this issue of Molecular Therapy) at Codiak BioSciences rigorously sought membrane-associated proteins that are highly expressed and enriched in EVs and thus well suited for novel applications in EV engineering. They identify members of the EWI immmunoglobulin and MARCKS families that appear to be strikingly versatile “scaffolds” for loading cargo ranging from cytokines to Cas9 to antigens. Furthermore, they bioengineer the top candidates for stability and test them in vivo. 2The delivery potential of EVs has been recognized since EV studies first coalesced into a field. Prototypes for EV engineering were presented in 2005 at the first international meeting on EV biology, organized by Rose Johnstone. With the goal of “targeted delivery of vesicles bearing new ligands or antibodies to specific tissues,” Delcayre et al. 3 of Anosys expressed soluble proteins as fusions with the C1C2 domain of lactadherin (MFGE8). Lactadherin traffics to the endosomal compartment in certain cells and is incorporated into EVs of the multivesicular body, known upon release as “exosomes”(in contrast to plasma membrane-derived “ectosomes”). This “exosome display” technology was used to decorate EVs with the HIV-1 Nef protein, interleukin 2 (IL-2), and granulocyte/monocyte colony-stimulating factor (GM-CSF), with retention of biological activity and opportunities for eliciting immune responses.