A System Based on Novel Parainfluenza Virus PIV5-L for Efficient Gene Delivery of B-Lymphoma Cells

Abstract

B-cell lymphoma is a common aggressive neoplastic disorder of lymphocytes. Delivery of genes of interest into B cells, particularly virus-mediated B-lymphoma cells, is still a challenge. In this study, we report that a system (L-VLP) based on the parainfluenza virus PIV5-L strain isolated from B cells had highly expressed exogenous genes and remained stable without obvious cell toxicity, which provides a potential new strategy for gene delivery and treatment of B-cell cancer.

Virus-like particle – mediated delivery of the RIG-I agonist M8 induces a type I interferon response and protects cells against viral infection

“…These observations support the growing body of studies that identifies VLPs as a intriguing system for targeted therapies: several models have been developed not only in vaccination strategies, where the expression of selective antigen domains elicit the production of neutralizing antibodies ( Zha et al., 2021 ), but also for the delivery of therapeutic molecules by expressing ligands for specific receptors overexpressed in tumor cells ( Pokorski et al., 2011 ; Kitai et al., 2011 ; Galaway and Stockley, 2012 ; Liu et al., 2022 ) or for gene editing applications ( Banskota et al., 2022 ). Overall, in this study we have demonstrated several key points that make the VLPs-M8 system a promising platform for a potential clinical use: I) Inclusion – we demonstrated that HIV-1 - based packaging system incorporated and protected M8 for intracellular release; II) Delivery M8 was efficiently transferred to target cells where it triggered a RIG-I – dependent type-I IFN response that drastically reduced or completely blocked viral replication; III) Versatility and Specificity – one of the most important advantages of this system is its flexibility; indeed VLPs surface modifications guide VLPs to a selective cell population expressing a specific receptor.…”

Parainfluenza virus 5 is a next‐generation vaccine vector for human infectious pathogens

“…69 This hypothesis was further supported by theoretical and experimental evidence, including strains isolated from a variety of human tissues on numerous occasions. [76][77][78] A recent report showed that a novel PIV5 strain was isolated from a lesser panda, which was closely related to the zoo tiger PIV5 strains isolated in China in 2015 and 2018. 79 Subsequently, two more PIV5 strains were identified in pangolins in China.…”

“…Based on this, it was speculated that infection of monkeys may occur either in transit or shortly after contact with humans 69 . This hypothesis was further supported by theoretical and experimental evidence, including strains isolated from a variety of human tissues on numerous occasions 76–78 …”

“…65 Moreover, the production of replicon-containing VLPs has also been simplified from the previous two-step process to a one-step process. 76 In the case of the PIV5-respiratory syncytial virus (RSV) vaccine, for example, the modified PIV5 only deletes the three structural proteins (M, NP, and HN proteins) to make PIV5-AVLP and the AVLP-based vaccine expressing RSV F generates robust antigenspecific immune responses and protects against RSV infection in mice, indicating that PIV5-AVLP-vectored RSV vaccines show promising potentials as effective RSV vaccines. 66 To make the PIV5 vector a safer and easier vaccine candidate, modification of the vector and improvement of the production process continue to be developed.…”

“…123 Immunity against PIV5 vectors has also revealed new possibilities for the development of antitumor or multipathogen vector vaccines. 76 However, the known preexisting immunity to PIV5 raises the question of its efficacy as a vaccine vector. Previous research has found that rPIV5 expressing HA is immunogenic in dogs with prior PIV5 exposure, indicating that PIV5-based vaccines can overcome pre-existing immunity to PIV5.…”