A Comparative Study on Delivery of Externally Attached DNA by Papillomavirus VLPs and Pseudoviruses.
A Comparative Study on Delivery of Externally Attached DNA by Papillomavirus VLPs and Pseudoviruses.
复制标题
DOI：
10.3390/vaccines9121501
复制
发表时间：
2021-12-18
期刊：
影响因子：
7.8
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Brendle S;Cladel N;Balogh K;Alam S;Christensen N;Meyers C;Hu J
人乳头瘤病毒（HPV）16衣壳在许多研究中已被选择作为DNA递送载体。我们的初步研究表明，HPV 58衣壳可能是比HPV 16衣壳更好的载体，以提供体外和体内包裹的DNA。在目前的研究中，我们比较了HPV 16，HPV 58和棉尾兔乳头瘤病毒（CRPV）衣壳作为L1/L2 VLP或假病毒（PSV）提供外部附着的GFP表达DNA。兔子和人类细胞都被用来测试是否存在物种特异性效应。通过流式细胞术定量GFP表达细胞群或平均荧光强度（MFI）来确定DNA递送效率。有趣的是，与16-VLP和PSV相比，CRPV和58-VLP和PSV在递送附着的DNA方面显著更有效。衣壳/DNA比率为2：1显示出递送外部DNA的最高效率。携带乳头瘤病毒DNA的PSV也比携带无关质粒DNA的PSV表现出更高的效率。与HPV 58 L1/16 L2 VLP相比，HPV 16 L1/58 L2杂交VLP显示出更高的效率，这表明L2可能在递送附着DNA中发挥关键作用。此外，我们证明了VLP增加了CRPV DNA在兔体内的感染性。我们的结论是，选择CRPV或58衣壳提供外部DNA可以提高在体外和体内模型中的DNA摄取。
Human papillomavirus (HPV) 16 capsids have been chosen as a DNA delivery vehicle in many studies. Our preliminary studies suggest that HPV58 capsids could be better vehicles than HPV16 capsids to deliver encapsidated DNA in vitro and in vivo. In the current study, we compared HPV16, HPV58, and the cottontail rabbit papillomavirus (CRPV) capsids either as L1/L2 VLPs or pseudoviruses (PSVs) to deliver externally attached GFP-expressing DNA. Both rabbit and human cells were used to test whether there was a species-specific effect. DNA delivery efficiency was determined by quantifying either GFP-expressing cell populations or mean fluorescent intensities (MFI) by flow cytometry. Interestingly, CRPV and 58-VLPs and PSVs were significantly more efficient at delivering attached DNA when compared to 16-VLPs and PSVs. A capsid/DNA ratio of 2:1 showed the highest efficiency for delivering external DNA. The PSVs with papillomavirus DNA genomes also showed higher efficiency than those with irrelevant plasmid DNA. HPV16L1/58L2 hybrid VLPs displayed increased efficiency compared to HPV58L1/16L2 VLPs, suggesting that L2 may play a critical role in the delivery of attached DNA. Additionally, we demonstrated that VLPs increased in vivo infectivity of CRPV DNA in rabbits. We conclude that choosing CRPV or 58 capsids to deliver external DNA could improve DNA uptake in in vitro and in vivo models.
登录
查看更多内容
影响因子：
15.9
作者：
Cuburu, Nicolas;Graham, Barney S.;Schiller, John T.
通讯作者：
Schiller, John T.
影响因子：
13.2
作者：
Cladel, Nancy M.;Jiang, Pengfei;Hu, Jiafen
通讯作者：
Hu, Jiafen
影响因子：
5.4
作者：
Holmgren, SC;Patterson, NA;Lambert, PF
通讯作者：
Lambert, PF
影响因子：
3.1
作者：
Cladel, Nancy M.;Hu, Jiafen;Christensen, Neil D.
通讯作者：
Christensen, Neil D.
影响因子：
5.4
作者：
Buck, Christopher B.;Cheng, Naiqian;Trus, Benes L.
通讯作者：
Trus, Benes L.