Peking University scholar NAR publishes paper: Development of RNA nanomaterials that interfere with HIV-1 virus assembly

Recently, the research group of Chen Kuangshi, Department of Biomedical Engineering, School of Future Technology, based on RNA nanotechnology, developed an RNA nanomaterial that can interfere with the assembly of HIV-1 virus on the cell membrane
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The research results have been published in the academic journal Nucleic Acids Research (IF = 16.

Gag protein, an important structural protein of HIV-1 virus, is an RNA-binding protein that can interact with the viral genome RNA (gRNA) and use it as a scaffold to multimerize on the cell membrane and finally assemble to form virus particles
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So far, a large number of research results have proved that in addition to viral RNA, Gag protein can also form RNA-protein complexes with various host cell RNAs.
) can interact with Gag protein, and can compete with viral RNA-Gag protein interaction on the cell membrane, thereby interfering with viral RNA-mediated Gag protein multimerization, resulting in the failure of viral particle assembly [ Proc Natl Acad Sci USA .

Compared with natural small RNAs, artificially synthesized RNA oligonucleotides have the advantages of high adjustability and controllability in terms of base composition, molecular size, structure and chemical modification, and can be assembled by RNA nanotechnology to form more The complex nanostructure is a nanomaterial with high modifiability, good stability and high biosafety
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Based on the previous research on natural small RNAs, this work uses artificially synthesized 2'-O-Methyl modified RNA oligonucleotides as raw materials, and develops a modular RNA nanomaterial through self-assembly technology.

In this study, the research group first found that compared with RNA oligonucleotides without a specific structure, Gag protein has a higher binding tendency to oligonucleotides that can form hairpin structures on the cell membrane, and this binding tendency It is not dependent on the specific base sequence (sequence-independent)
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The interaction of Gag with hairpin RNA can significantly inhibit HIV-1 virion production (Fig.

Figure 1.
The RNA oligonucleotide with hairpin structure (STL1) has a stronger interaction with Gag protein on the cell membrane than the unstructured oligonucleotide (UN1), thereby effectively inhibiting the production of HIV-1 virus particles

Figure 2.
Self-assembly of multiple oligonucleotides with hairpin structures to obtain nanostructures that interfere more with HIV-1 assembly

Qu Na, a graduate doctoral student in Chen Kuangshi's research group, is the first author of this work.
Ying Yachen, a doctoral student in the research group, and Qin Jinshan, a postdoctoral fellow in the research group, made important contributions to the smooth completion of the work.
Chen Kuangshi is the corresponding author of this work
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This work was supported by the National Key R&D Program and the National Natural Science Foundation of China