Towards access for all: 1st Working Group Report for the Global Gene Therapy Initiative (GGTI)

The gene and cell therapy field saw its first approved treatments in Europe in 2012 and the United States in 2017 and is projected to be at least a $10B USD industry by 2025. Despite this success, a massive gap exists between the companies, clinics, and researchers developing these therapeutic approaches, and their availability to the patients who need them. The unacceptable reality is a geographic exclusion of low-and middle-income countries (LMIC) in gene therapy development and ultimately the provision of gene therapies to patients in LMIC. This is particularly relevant for gene therapies to treat human immunodeficiency virus infection and hemoglobinopathies, global health crises impacting tens of millions of people primarily located in LMIC. Bridging this divide will require research, clinical and regulatory infrastructural development, capacity-building, training, an approval pathway and community adoption for success and sustainable affordability. In 2020, the Global Gene Therapy Initiative was formed to tackle the barriers to LMIC inclusion in gene therapy development. This working group includes diverse stakeholders from all sectors and has set a goal of introducing two gene therapy Phase I clinical trials in two LMIC, Uganda and India, by 2024. Here we report on progress to date for this initiative

A mathematical model of HIV dynamics in the presence of a rescuing virus with replication deficiency

Recently, an enzyme (Cre recombinase) has been developed by directed evolution that successfully removes the HIV genome from the nuclear DNA of infected cells. To explore this idea further, we hypothesized that a replication deficient virus (called "police virus"), added externally, can deliver such a recombinase which excises the integrated HIV DNA from the genome of infected cells. Such a "police virus" could attack and remove the integrated provirus which is not possible using contemporary strategies. The hypothesis was tested by developing a mathematical model that describes the dynamics of virus-host cell interaction and the consequences of introducing the "police virus". The simulations show that such a therapeutic vector may eradicate all HIV viruses from the system in the long term. All components of the HIV infection (free virus, latently, and actively infected cells) can be cleared and the system ends up only with susceptible CD4+ cells. The proposed model may provide new insights in the dynamical behavior and future alternative treatments of HIV