Cascade amplification of therapeutic payloads for cancer immunotherapy.

ABSTRACT: Achieving sufficient therapeutic payload delivery remains a significant challenge in gene therapy, particularly for cancer immunotherapy, where payload thresholds are critical for efficacy. To address this, we developed a Cascade Amplification of Therapeutic Payloads (CATP) system, leveraging lipid nanoparticles (LNPs) to co-deliver self-amplifying mRNA (SamRNA) and modified mRNA encoding alphavirus capsids and envelopes. The CATP system initiates a dual-amplification process: SamRNA amplifies therapeutic payloads within transfected cells, while capsid and envelope proteins package SamRNA into defective viral particles to infect neighboring cells, enabling secondary payload amplification. This single-cycle infection ensures enhanced efficacy while maintaining safety. In vitro and in vivo s

SUBMITTER: Li Y 

PROVIDER: S-EPMC12375736 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature