George leads Synthetic Biology at the Wyss Institute, where he oversees the directed evolution of molecules, polymers, and whole genomes to create new tools with applications in regenerative medicine and bio-production of chemicals. Among his recent work at the Wyss is development of a technology for synthesizing whole genes, and engineering whole genomes, far faster...
The Church lab is working on gene and cell therapies for age-related and infectious diseases. Their priorities are to build a mechanism to create resistance to all viruses and radiation, enhance organs via gene therapy, create a better method for multiplex editing, and finally to reverse aging and improve gene/cell therapies.
Reading and writing DNA has been exponentially improving. What the field is driving toward is a one per lifetime or per decade treatment, with extremely low cost at scale (roughly $2 per dose) and minimal off-target effects. Gene therapy, when done right, is far superior to small molecule drug therapy. Church and his lab are working on using multiplexed genome engineering to create multi-virus resistance at the genomic level. Recoding two serine codons into leucine codons in a specific section of the genome causes general resistance to viruses as demonstrated by testing against a dozen environmental phage isolates.
You may have heard about the recent transplantation of a modified pig heart into a human. This was made possible through extensive modifications to the genome of the pig, changing its biology to prevent immune reactions in the human body. Sugars, clotting factors, immune functions, major histocompatibility, and porcine endogenous retroviruses all created issues for xenotransplantation. The sheer volume of genome editing required to modify these traits was only recently made possible as gene therapy has scaled in efficiency.
This new scale of editing can be used to confer resistance to pathogens, cancer, senescence, immunity, cryopreservation, dehydration, and DNA-damage to humans. It can also be used to tackle long and short interspersed nuclear elements (LINE, SINE) that have been associated with aging. With this level of editing it may be possible to target most of the hallmarks of aging by modifying things like FGF21, Klotho, and TGF-B. Currently, AAV and CMV are used as delivery vectors for these early therapeutic experiments. We will need to advance beyond these early, low-efficiency methods to get to gene therapies.
Improve multiplex gene editing methods
Improve delivery mechanisms of gene therapies
Create $2 per dose gene therapy that hits 90%+ of target cells in a clinical setting