A team of researchers at the University of Waterloo in Canada is using RNA technology to open up a new way to fight the human immunodeficiency virus (HIV). A research team led by Emmanuel Ho, an associate professor of pharmacy at the university, has developed an innovative nanomedicine that contains genetic material called small interfering RNAs (siRNAs). These siRNA molecules are effective in regulating the expression of specific genes or proteins within cells, and have been shown to significantly reduce HIV replication by up to 73%.
这项突破性研究成果，题为“pH-sensitive dual-preventive siRNA-based nanomicrobicide reactivates autophagy and inhibits HIV infection in vaginal CD4+ cells”，已在《控制释放杂志》上发表。
doi: 10.1016/j.jconrel.2023.12.043
"This discovery opens up a new avenue for research into new therapies to combat HIV," said Dr. Ho. He is one of the leaders of the University of Waterloo in the field of health innovation in Canada.
Autophagy, the self-recycling process of cells, is essential for the removal of microorganisms such as viruses and bacteria from the cells. The HIV virus skillfully inhibits the autophagic function of cells by producing the Nef protein.
This study is the first to develop a composite nanomedicine that not only reactivates autophagy, but also prevents the HIV virus from entering cells, thereby restoring the body's own defense mechanisms.
In addition, the CCR5 gene of the HIV virus is key to its invasion of cells. The siRNA molecule in study targets both the Nef protein and the CCR5 gene to reduce HIV infection rates.
This nanomedicine is designed to be administered vaginally to prevent sexual transmission of HIV. The drug remains stable in an acidic vaginal environment and does not leak siRNA until it enters the interior of the cell.
"Viruses are very cunning, and they stop autophagy by producing the Nef protein," Dr. Ho explains. "Our approach enables the body to effectively fight viral infections without relying on additional medications."
Dr. Ho confirmed that the next research work will include further optimizing this process and deepening the understanding of the role of autophagy in cellular antiviral protection.
"We also hope that this study will provide new ideas for the development of more alternative therapies to reduce antimicrobial resistance," Dr Ho said.
Outline of Research
HIV/AIDS is a global health problem, and although existing antiretroviral treatments can control viral replication, they are not completely eliminated and drug resistance is a problem.
Autophagy is an intracellular clean-up and recycling mechanism that is essential for maintaining cellular homeostasis. Studies have shown that HIV is able to inhibit autophagy in host cells, thereby promoting viral replication.
siRNAs, as a gene silencing technique, are able to specifically inhibit the expression of specific genes. In HIV treatment, siRNAs can be used to target key genes of the virus, thereby inhibiting viral replication.
Research Objectives and Innovations
This study aims to develop a novel nanomedicine that targets key genes of HIV through siRNA while activating the autophagic mechanism of host cells to enhance cellular resistance to HIV.
The innovation lies in the design of a pH-sensitive nanocarrier that is stable in the acidic environment of the vagina and releases siRNA upon entry into the cell, which can improve the targeting and bioavailability of the drug.
methodology
Specific siRNAs were synthesized and encapsulated in pH-sensitive nanocarriers.
In vitro experiments were carried out to test the stability and release characteristics of nanomedicines at different pH values.
Using a cellular model of HIV infection, the effect of nanomedicine in activating autophagy and inhibiting HIV replication was evaluated.
Findings:
Nanopharmaceuticals exhibit good stability under acidic conditions and are able to efficiently release siRNA within cells.
In vaginal CD4+ cells, nanodrugs can significantly activate autophagy and inhibit HIV infection.
Discussion & Significance
The findings suggest that this nanomedicine has the potential to be an effective HIV prevention strategy, especially in the prevention of sexual transmission.
By activating autophagy, this strategy may provide new avenues for HIV treatment, especially in the fight against drug-resistant strains.
Future research needs to further explore the safety, biodistribution, and efficacy of this nanomedicine in animal models.
Conclusions
This study provides a novel siRNA-based nanomedicine that has shown the potential to inhibit HIV infection in an in vitro model.
The development of this drug provides new ideas for the prevention and treatment of HIV, especially in terms of harnessing the defense mechanisms of the host cells themselves.