THERAPEUTIC INTERFERING PARTICLES
(A.K.A. TIPs)
Beginning in the early 2000s, our group put forward the theory for a new class of antiviral countermeasure called Therapeutic Interfering Particles (often referred to as ‘TIPs’) – see TED talk which recounts some of the history.
TIPs were conceived to address ‘universal’ challenges in infectious disease control faced by virtually all current interventions. These challenges include:
(i) Deployment (e.g. reaching the highest-risk, infectious ‘superspreaders’ who drive disease circulation)
(ii) Pathogen persistence & behavioral barriers (e.g. adherence)
(iii) Evolution (e.g. resistance and escape)
These barriers exist because pathogens are dynamic—they mutate and transmit—while existing therapies are static, neither mutating nor transmitting.
To surmount these barriers, we proposed a radical shift in therapeutic paradigm toward developing adaptive, dynamic therapies (Metzger et al. 2011). Building off data-driven epidemiological models, we showed that engineered molecular parasites, designed to piggyback on HIV-1, could circumvent each barrier and dramatically lower HIV/AIDS in sub-Saharan Africa as compared to established interventions. These molecular parasites became known as TIPs.
These molecular parasites essentially steal replication and packaging resources from HIV within infected cells thereby generating Therapeutic Interfering Particles (TIPs)[1] which deprive HIV of critical replication machinery thereby reducing viremia. The fundamental departure from conventional therapies is that TIPs are under strong evolutionary selection to maintain parasitism with HIV and will thus co-evolve with HIV, establishing a co-evolutionary ‘arms race’ (Rouzine and Weinberger, 2013).
Like Oral Polio Vaccine, (OPV)—currently used for the W.H.O. worldwide polio-eradication effort—TIPs could also transmit between individuals, a recognized benefit for OPV. TIP transmission would occur along HIV-transmission routes (via identical risk factors), thereby overcoming behavioral issues and automatically reaching high-risk populations to limit HIV transmission even in resource-poor settings.
For review: Notton et al. Current Opinion in Biotechnology 2014.
Papers of note: Metzger, Lloyd-Smith, and Weinberger. PLoS Computational Biology 2011 (videos above) and Rouzine and Weinberger. Journal of Virology 2013 (Linked above).
[1] TIPs are a distinct form of defective interfering particles (DIPs) engineered to have a basic reproductive ratio (R0) > 1.