A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma.
A GATA3 Targeting Nucleic Acid Nanocapsule for In Vivo Gene Regulation in Asthma.
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DOI：
10.1021/acsnano.0c07781
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发表时间：
2021-07-27
期刊：
影响因子：
17.1
通讯作者：
Rouge, Jessica L.
中科院分区：
文献类型：
--
作者：
Gavitt, Tyler D.;Hartmann, Alyssa K.;Sawant, Shraddha S.;Mara, Arlind B.;Szczepanek, Steven M.;Rouge, Jessica L.
过敏性哮喘是全世界儿童和成人的主要慢性肺部疾病之一，导致受影响个体的显着发病率和死亡率。许多患者患有严重的哮喘，这种哮喘难以治疗，这说明需要开发针对这种疾病的新疗法。在此，我们描述了使用肽交联核酸纳米胶囊 (NAN) 将 GATA3 特异性 DNAzyme 递送至免疫细胞，并证明了这些细胞的转录活性和行为受到调节。 NAN 由肽交联表面活性剂制成，其化学设计可在炎症条件下降解，响应蛋白水解酶释放单个 DNAzyme-表面活性剂缀合物。使用 NAN，GATA3 DNAzyme 被有效地递送至人外周血单核细胞，并有明确的证据表明 CD4+ 辅助 T 细胞无需使用刺激性转染剂即可摄取。 GATA3 的敲低是使用人 Jurkat T 细胞在体外实现的，该细胞在稳态条件下表达 GATA3。此外，根据肺嗜酸性粒细胞增多症的测量，在屋尘螨 (HDM) 诱发的哮喘期间接受 DNAzyme-NAN 治疗的小鼠比仅使用 HDM 的对照小鼠出现的过敏性肺部炎症较轻。这项研究表明，肽交联的 GATA3 DNAzyme-NAN 可能有可能降低人类患者哮喘症状的严重程度，并且该技术用于人类的开发值得进一步研究。
Allergic asthma is one of the leading chronic lung diseases of both children and adults worldwide, resulting in significant morbidity and mortality in affected individuals. Many patients have severe asthma, which is refractory to treatment, illustrating the need for the development of new therapeutics for this disease. Herein, we describe the use of a peptide cross-linked nucleic acid nanocapsule (NAN) for the delivery of a GATA3-specific DNAzyme to immune cells, with demonstration of modulated transcriptional activity and behavior of those cells. The NAN, built from peptide cross-linked surfactants, is chemically designed to degrade under inflammation conditions releasing individual DNAzyme-surfactant conjugates in response to proteolytic enzymes. Using the NAN, GATA3 DNAzymes were delivered efficiently to human peripheral blood mononuclear cells, with clear evidence of uptake by CD4+ helper T cells without the need for harsh transfection agents. Knockdown of GATA3 was achieved in vitro using human Jurkat T cells, which express GATA3 under homeostatic conditions. Additionally, mice treated with DNAzyme-NANs during house dust mite (HDM)-induced asthma developed less severe allergic lung inflammation than HDM-only control mice, as measured by pulmonary eosinophilia. This study suggests that peptide cross-linked GATA3 DNAzyme-NANs may have the potential to decrease the severity of asthma symptoms in human patients, and development of this technology for human use warrants further investigation.
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通过反义诱导的GATA-3表达的局部阻断来治疗过敏性气道炎症和反应性过高。
影响因子：
15.3
作者：
Finotto, S;De Sanctis, G T;Lehr, H A;Herz, U;Buerke, M;Schipp, M;Bartsch, B;Atreya, R;Schmitt, E;Galle, P R;Renz, H;Neurath, M F
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影响因子：
64.8
作者：
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通讯作者：
Storhoff, JJ
影响因子：
2.9
作者：
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通讯作者：
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影响因子：
3.2
作者：
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Garn, Holger
影响因子：
14.2
作者：
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通讯作者：
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