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Targeted Delivery of siRNA Nanoparticles to Prevent HIV-1 Transmission

Targeted Delivery of siRNA Nanoparticles to Prevent HIV-1 Transmission
靶向递送 siRNA 纳米颗粒以预防 HIV-1 传播
批准号：
7554936
负责人：
Weidong Xu
金额：
$18.15万
依托单位：
TRANSGENEX NANOBIOTECH, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
项目状态：
已结题
起止时间：
2008-09-01 至 2009-11-30
来源：
https://reporter.nih.gov/project-details/7554936
关键词：
AIDS VaccinesAIDS/HIV problemAbbreviationsAcquired Immunodeficiency SyndromeAdverse effectsAgeAntibodiesAntiviral AgentsAttenuated Live Virus VaccineBiopolymersCCR5 geneCellsChildChitosanClinicalComplexDataDendritic CellsDevelopmentDiseaseDrug Delivery SystemsEnsureEnzyme-Linked Immunosorbent AssayFutureGene SilencingGenesGoalsHIVHIV-1HumanIn VitroInfectionInvestigationJointsLast NameLifeLungMacacaMalignant NeoplasmsMeasuresMedicineModelingMonkeysMonoclonal AntibodiesMononuclear LeukocytesMusNaturePTPN11 genePeripheral Blood Mononuclear CellPhasePhase II Clinical TrialsPhase III Clinical TrialsPolymerase Chain ReactionPreventionProphylactic treatmentRNARNA InterferenceResearchResearch PersonnelRespiratory Syncytial Virus InfectionsRespiratory Tract InfectionsRespiratory syncytial virusSmall Interfering RNASmall RNASpecificityStagingSystemT-LymphocyteTechnologyTestingTherapeuticTimeTransfectionTranslatingUnited NationsVaccinesViralViral CancerViral GenesVirusVirus DiseasesWorkairway inflammationatrial natriuretic factor receptor Abasedayenv Genesmelanomamouse modelnanoparticlenonhuman primatenovelperipheral bloodpreclinical studypreventprogramsrespiratorysimian human immunodeficiency virussuccesstargeted deliverytooltransmission process

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DESCRIPTION (provided by applicant): According to estimates by the Joint United Nations Program on HIV/AIDS (UNAIDS), approximately 40 million people will be living with HIV/AIDS worldwide by the end of 2006. However, safe and effective AIDS vaccine remains difficult to develop. Small interference RNA (siRNA) has emerged as a powerful tool in gene silencing, and appears promising in treatment of viral infections and cancers. The combination of siRNA and chitosan nanoparticle technology led to the development nanocomplex antivirals capable of inhibiting respiratory syncytial virus infections (Zhang et. al. Nature Medicine, 2005). Based on the preliminary in vitro data for suppressing HIV replication, it is hypothesized that siRNA nanocomplexes comprise a potential therapeutic approach against AIDS. The long-term goal of our proposal is to develop multifunctional siRNA nanoparticles to protect HIV transmission. However, we will only test the antiviral activities of the multifunctio intensified, since a safe and effective AIDS vaccine remains difficult to develop and won't be available in this decade. Small interfering RNA (siRNA) has emerged as a powerful tool in gene silencing, and preclinical studies have shown promise in treatment of viral infection and cancer. The potential of siRNA for inhibiting respiratory infections has been demonstrated using a nanoparticle delivery system in a mouse model of respiratory syncytoial virus (RSV) infection. Intranasal treatment before or after RSV infection with nanoparticles containing siRNA targeting the NS1 gene of RSV showed substantially decreased virus titers in the lung and decreased inflammation and airway reactivity compared to controls. These results have led to the working hypothesis that multifunctional chitosan nanoparticles (MCNs) can effectively deliver siRNA without any significant adverse effects and provide significant protection against viral infections, specifically HIV. The specific aims of this proparticles in inhibiting SHVSF163P3 replication in human or monkey peripheral blood mononuclear leukocytes (PBMCs). In vitro confirmation of the antiviral activity of the multifunctional siRNA nanoparticles will ensure the success in future studies in non-human primates. The proposed project is significant, successful delivery of anti-HIV siRNA nanoparticles to prevent HIV-1 replication in vitro will help us in non-human primate studies or preclinical trials in the future. Thus, the novel chitosan nanoparticle drug delivery system will be useful not only in AIDS research but also in studies in cancer and other diseases
期刊论文(1)
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会议论文
A Multiple siRNA-Based Anti-HIV/SHIV Microbicide Shows Protection in Both In Vitro and In Vivo Models.
DOI： 10.1371/journal.pone.0135288
发表时间： 2015
期刊： PloS one
影响因子： 3.7
作者： [Boyapalle S, Xu W, Raulji P, Mohapatra S, Mohapatra SS]
通讯作者： Mohapatra SS
Systemic delivery of an oncolytic adenovirus targeting TGFβ to enhance anti-PD-1 and anti-CTLA-4 therapy for triple negative breast cancer
Systemic delivery of an oncolytic adenovirus targeting TGFβ to enhance anti-PD-1 and anti-CTLA-4 therapy for triple negative breast cancer
Systemic delivery of an oncolytic adenovirus targeting TGFβ to enhance anti-PD-1 and anti-CTLA-4 therapy for triple negative breast cancer