%0 Journal Article
%T Systemically targeted cancer immunotherapy and gene delivery using transmorphic particles.
%A Asavarut P
%A Waramit S
%A Suwan K
%A Marais GJK
%A Chongchai A
%A Benjathummarak S
%A Al-Bahrani M
%A Vila-Gomez P
%A Williams M
%A Kongtawelert P
%A Yata T
%A Hajitou A
%J EMBO Mol Med
%V 14
%N 8
%D 08 2022 8
%M 35758207
%F 14.26
%R 10.15252/emmm.202115418
%X Immunotherapy is a powerful tool for cancer treatment, but the pleiotropic nature of cytokines and immunological agents strongly limits clinical translation and safety. To address this unmet need, we designed and characterised a systemically targeted cytokine gene delivery system through transmorphic encapsidation of human recombinant adeno-associated virus DNA using coat proteins from a tumour-targeted bacteriophage (phage). We show that Transmorphic Phage/AAV (TPA) particles provide superior delivery of transgenes over current phage-derived vectors through greater diffusion across the extracellular space and improved intracellular trafficking. We used TPA to target the delivery of cytokine-encoding transgenes for interleukin-12 (IL12), and novel isoforms of IL15 and tumour necrosis factor alpha (TNF α ) for tumour immunotherapy. Our results demonstrate selective and efficient gene delivery and immunotherapy against solid tumours in vivo, without harming healthy organs. Our transmorphic particle system provides a promising modality for safe and effective gene delivery, and cancer immunotherapies through cross-species complementation of two commonly used viruses.