Respiratory Syncytial Virus (RSV) has been a major health concern globally for decades, yet no effective prophylactic or treatment regimen is available. The key viral proteins responsible for RSV pathology include the fusion protein (F), the immunomodulatory non-structural-protein 1 (NS1) and the Phosphoprotein (P) involved in viral replication. Herein, we developed a novel shell-core multifunctional nanosystem with dual payload: a plasmid construct encoding for shRNAs against NS1 and P, and an anti-fusion peptide (HR2D). Anti-ICAM1 antibody conjugated on the nanoparticle (NP) surface is used to target RSV infected cells. Our data show the potential of this nanosystem as a prophylactic and/or a therapeutic regimen against RSV infection. Furthermore, therapy of RSV infected mice with this nanosystem, in addition to reducing viral load, modulated expression of Th2 and allergy-associated cytokines such as IL4, IL-13 and IL-17 indicating a direct role of this nanosystem in the mechanisms involved in the immunoregulation of disease pathogenesis.

几十年来，呼吸道合胞病毒（RSV）一直是全球主要的健康问题，但尚无有效的预防或治疗方案。负责 RSV 病理学的关键病毒蛋白包括融合蛋白 (F)、免疫调节非结构蛋白 1 (NS1) 和参与病毒复制的磷酸蛋白 (P)。在此，我们开发了一种具有双重有效负载的新型壳核多功能纳米系统：编码针对 NS1 和 P 的 shRNA 的质粒构建体，以及抗融合肽（HR2D）。纳米颗粒 (NP) 表面缀合的抗 ICAM1 抗体用于靶向 RSV 感染的细胞。我们的数据显示了该纳米系统作为针对 RSV 感染的预防和/或治疗方案的潜力。此外，用该纳米系统治疗 RSV 感染的小鼠，除了减少病毒载量外，还调节 Th2 和过敏相关细胞因子（如 IL4、IL-13 和 IL-17）的表达，表明该纳米系统在涉及的机制中具有直接作用。疾病发病机制的免疫调节。