Engineering microbiomes with CRISPR to improve our climate and health

Problem

We live in a microbial world. Microbes — the broad name given to microscopic organisms, including bacteria, fungi and viruses — live in communities called “microbiomes” in, on and around us. Microbiomes are found on our skin and in our guts, in plants and animals, as well as in the water, air and ground,  shaping human and animal biology and the larger world. There is an ever-growing list of health issues attributed to microbiome imbalance or dysregulation, including obesity, asthma, cardiovascular disease and neurological disorders like Alzheimer’s disease. These issues affect hundreds of millions of people, a disproportionate number of them people of color and those living in low-income communities. At the same time, microbiomes in livestock, agricultural soils and other environmental sources generate a significant source of global greenhouse gas emissions, such as methane and nitrous oxide. These are among the leading causes of climate change — affecting us all.

Big Idea

The team at Innovative Genomics Institute is building on two state-of-the-art toolsets — CRISPR genome editing, which enables the precision editing of DNA, and genome-resolved metagenomics, which provides a complete picture of every organism in a microbiome and the function of its genes — to create a revolutionary new approach. Their idea is to edit the genomes of microbiomes as a solution to seemingly insurmountable health and climate problems. By establishing a “genomic microbiome engineering” platform, they will build a whole new class of interventions — and take a significant step toward a future in which doctors have new ways to treat and prevent incurable diseases, and in which humanity has new tools for reducing greenhouse gas emissions and reaching global climate goals.

Plan

Over the next seven years, the Innovative Genomics Institute will inaugurate this new field by focusing on two specific, real-world interventions: one to bring relief from childhood asthma, a currently intractable disease that affects 300 million people globally, as well as a new mitigation strategy to curb agricultural methane emissions, a greenhouse gas that has more than 80 times the warming power of carbon dioxide. While developing these interventions, they will discover new microbiome editing and delivery tools, use what they learn to develop and test strategies that enable genome engineering in increasingly complex systems, and work with partners to conduct clinical and field trials to prove safety and efficacy. But perhaps most importantly, they will disseminate their learnings and tools to the wider research community, providing other scientists with access and evidence to scale this transformative approach.

Why will it succeed?

The Innovative Genomics Institute is the world’s premier genomic editing institution, housed at the University of California, Berkeley, with affiliated investigators at UC San Francisco (UCSF) and UC Davis. It brings together teams with demonstrated abilities to discover new solutions, translate them into actionable applications and responsibly guide the field, sharing with peers and co-creating standards for regulation and safety. Led by Dr. Jennifer Doudna and Dr. Jill Banfield — pioneers in genome editing and metagenomics, respectively — IGI specifically selects issues where the severity and total number of people affected is high, with disproportionate impact on underserved communities. In 2021, for example, IGI collaborated with UCSF and University of California, Los Angeles (UCLA), to launch the first fully nonprofit clinical trial to treat sickle cell disease, with a CRISPR-based therapy designed to correct a mutation in patients’ cells. If successful, this could be a far more advanced approach than exists today, reaching more people at lower cost.