Long noncoding RNAs (lncRNAs) play multiple key regulatory roles in various cellular pathways. However, their functions in HIV-1 latent infection remain largely unknown. Here we show that a lncRNA named NRON, which is highly expressed in resting CD4+ T lymphocytes, could be involved in HIV-1 latency by specifically inducing Tat protein degradation. Our results suggest that NRON lncRNA potently suppresses the viral transcription by decreasing the cellular abundance of viral transactivator protein Tat. NRON directly links Tat to the ubiquitin/proteasome components including CUL4B and PSMD11, thus facilitating Tat degradation. Depletion of NRON, especially in combination with a histone deacetylase (HDAC) inhibitor, significantly reactivates the viral production from the HIV-1-latently infected primary CD4+ T lymphocytes. Our data indicate that lncRNAs play a role in HIV-1 latency and their manipulation could be a novel approach for developing latency-reversing agents.

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Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumorassociated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8 + T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.

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