文獻(xiàn)：DOPC-Detergent Conjugates: Fusogenic Carriers for Improved In Vitro and In Vivo Gene Delivery

作者：Philippe Pierrat, Anne Casset, Dimitri Kereselidze, Marie Lux, Fran?oise Pons, Luc Lebeau

文獻(xiàn)鏈接：https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201600012

摘要：

Phospholipid-detergent conjugates are proposed as fusogenic carriers for gene delivery. Eleven compounds are prepared and their properties are investigated. The ability of the conjugates to promote fusion with a negatively charged model membrane is determined. Their DNA delivery efficiency and cytotoxicity are assessed in vitro. Lipoplexes are administered in the mouse lung, and transgene expression Indeterminate inflammatory activity are measured. The results show that conjugation of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with C12E4 produces a carrier that can efficiently deliver DNA to cells, with negligible ?associated toxicity. Fusogenicity of the conjugates shows good correlation with in vitro transfection efficiency and crucially depends on the length of the polyether moiety of the detergent. Finally, DOPC-C12E4 reveals highly potent for in vivo DNA delivery and favorably compares to GL67A, the current golden standard for gene delivery to the airway, opening the way for further promising developments.

磷脂洗滌劑偶聯(lián)物被提出作為基因遞送的融合載體。制備了11種化合物，并對(duì)其性質(zhì)進(jìn)行了研究。測定偶聯(lián)物促進(jìn)與帶負(fù)電荷的模型膜融合的能力。

在體外評(píng)估它們的DNA遞送效率和細(xì)胞毒性。在小鼠肺部施用Lipoplex，并測量轉(zhuǎn)基因表達(dá)不確定的炎癥活性。

結(jié)果表明，1,2-二油�；�-sn-甘油-3-磷酸膽堿（DOPC）與C12E4的偶聯(lián)產(chǎn)生了一種載體，可以有效地將DNA遞送到細(xì)胞，相關(guān)毒性可以忽略不計(jì)。

偶聯(lián)物的融合原性與體外轉(zhuǎn)染效率具有良好的相關(guān)性，并且在很大程度上取決于洗滌劑聚醚部分的長度。

最后，DOPC-C12E4在體內(nèi)DNA遞送方面表現(xiàn)出色，與目前用于氣道基因遞送的金標(biāo)準(zhǔn)GL67A相比具有優(yōu)勢，為進(jìn)一步有前景的發(fā)展開辟了道路。

相關(guān)推薦：

DOPE-PEG-CH2COOH

DOPE-PEG-FA

DOPE-PEG-Mal

DOPE-PEG-NH2

DOPE-PEG-SC

DOPE-PEI

DPPE-Cap-Biotin

DPPE-Cap-Folate

DPPE-ICG

DPPE-mPEG

DPPE-PEG2-NH-Mal

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