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一种在人铁蛋白表面展示的具有高中和活性的 SARS-CoV-2 纳米抗体。

A SARS-CoV-2 Nanobody Displayed on the Surface of Human Ferritin with High Neutralization Activity.

机构信息

National Key Laboratory of Agricultural Microbiology, Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, People's Republic of China.

College of Life Sciences, Capital Normal University, Beijing, People's Republic of China.

出版信息

Int J Nanomedicine. 2024 Mar 8;19:2429-2440. doi: 10.2147/IJN.S450829. eCollection 2024.

DOI:10.2147/IJN.S450829
PMID:38476285
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10929646/
Abstract

PURPOSE

COVID-19 is rampant throughout the world, which has caused great damage to human lives and seriously hindered the development of the global economy. Aiming at the treatment of SARS-CoV-2, in this study, we proposed a novel fenobody strategy based on ferritin (Fe) self-assembly technology.

METHODS

The neutralizing nanobody H11-D4 of SARS-CoV-2 fused to the C-terminus of end-modified human ferritin was expressed in and silkworm baculovirus expression systems. A large number of nanoparticles were successfully self-assembled in silkworms, while relatively few nanoparticles can be observed in the treated products from by electron microscopy. Subsequently, the fenobody's expression level and neutralizing activity were then evaluated.

RESULTS

The results showed that the IC of H11-D4 and fenobody Fe-H11-D4 expressed in were 171.1 nmol L and 20.87 nmol L, respectively. However, the IC of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L showing better neutralization activity.

CONCLUSION

Therefore, fenobodies can be well self-assembled in silkworm baculovirus expression system, and ferritin self-assembly technology can effectively improve nanobody neutralization activity.

摘要

目的

COVID-19 在全球范围内肆虐,对人类生命造成了巨大的破坏,严重阻碍了全球经济的发展。针对 SARS-CoV-2 的治疗,本研究提出了一种基于铁蛋白(Fe)自组装技术的新型 Fenobody 策略。

方法

将 SARS-CoV-2 的中和纳米抗体 H11-D4 融合到末端修饰的人铁蛋白的 C 末端,在 和家蚕杆状病毒表达系统中表达。在家蚕中成功地自组装了大量的纳米颗粒,而通过电子显微镜观察到的处理产物中相对较少的纳米颗粒。随后,评估了 Fenobody 的表达水平和中和活性。

结果

结果表明,在 中表达的 H11-D4 和 Fenobody Fe-H11-D4 的 IC 分别为 171.1 nmol L 和 20.87 nmol L,而在蚕中表达的 Fe-HD11-D4 的 IC 为 1.46 nmol L,表现出更好的中和活性。

结论

因此,Fenobodies 可以在家蚕杆状病毒表达系统中很好地自组装,铁蛋白自组装技术可以有效地提高纳米抗体的中和活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/44e07167adfa/IJN-19-2429-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/5f5af2e3a41f/IJN-19-2429-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/8299d9dfb566/IJN-19-2429-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/58c6e541c37b/IJN-19-2429-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/1ecc1e219c97/IJN-19-2429-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/44e07167adfa/IJN-19-2429-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/5f5af2e3a41f/IJN-19-2429-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/8299d9dfb566/IJN-19-2429-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/58c6e541c37b/IJN-19-2429-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/1ecc1e219c97/IJN-19-2429-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b8/10929646/44e07167adfa/IJN-19-2429-g0005.jpg

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