Therapeutic interfering particle

rdf:langString Therapeutic interfering particle

rdf:langString A therapeutic interfering particle is an antiviral preparation that reduces the replication rate and pathogenesis of a particular viral infectious disease. A therapeutic interfering particle is typically a biological agent (i.e., nucleic acid) engineered from portions of the viral genome being targeted. Similar to Defective Interfering Particles (DIPs), the agent competes with the pathogen within an infected cell for critical viral replication resources, reducing the viral replication rate and resulting in reduced pathogenesis. But, in contrast to DIPs, TIPs are engineered to have an in vivo basic reproductive ratio (R0) that is greater than 1 (R0>1). The term "TIP" was first introduced in 2011 based on models of its mechanism-of-action from 2003. Given their unique R0>1 mechanism of action, TIPs exhibit high barriers to the evolution of antiviral resistance and are predicted to be resistance proof. Intervention with therapeutic interfering particles can be prophylactic (to prevent or ameliorate the effects of a future infection), or a single-administration therapeutic (to fight a disease that has already occurred, such as HIV or COVID-19). Synthetic DIPs that rely on stimulating innate antiviral immune responses (i.e., interferon) were proposed for influenza in 2008 and shown to protect mice to differing extents but are technically distinct from TIPs due to their alternate molecular mechanism of action which has not been predicted to have a similarly high barrier to resistance. Subsequent work tested the pre-clinical efficacy of TIPs against HIV, a synthetic DIP for SARS-CoV-2 (in vitro), and a TIP for SARS-CoV-2 (in vivo).