Genome Editing: We often refer to a person’s genome – his complete set of genes – as a blueprint for life. But sometimes there are errors in this blueprint. Wouldn’t it be great if we could edit the blueprint and correct these errors? We might soon be able to. Researchers have developed tools that make it possible to cut an individual’s DNA in a specific location. Cellular enzymes then attempt to repair this break, but typically make mistakes in this repair, rendering the gene ineffective. This approach can be used to “knockout” a defective gene. This may sound like science fiction, but there are ongoing Phase II human clinical trials testing this technology’s ability to render human T-cells resistant to HIV. Sangamo also has positive preclinical data supporting the idea of using this technology to actually correct a gene sequence by co-delivering a “repair template” – a short piece of DNA containing the correct gene sequence which the cellular repair enzymes can then use to correct the defective gene sequence.
Immunotherapy: The term “immunotherapy” covers a wide range of topics, including vaccinations, monoclonal antibody therapeutics, stimulating a patient’s own immune system to fight cancer or other diseases, and using antibodies to deliver toxic compounds directly to cancer cells. Cancer vaccines are now being developed to target an individual’s own tumor antigens, activating the patient’s own immune system to target the tumor. Monoclonal antibodies now in development show promise as a potential treatment for Alzheimer’s disease by targeting the amyloid-beta plaques associated with disease progression. And antibody-drug conjugates, long in development, are now finally hitting the marketplace, enabling physicians to very specifically target cancer cells with highly toxic compounds.
Microbiome-Based Therapeutics: The premise behind microbiome-based therapeutics is straightforward: Identify differences in the microbiome of people suffering from a particular disease, and then try to make the sick person’s microbiome more like the healthy person’s.
Fecal transplants represent the blunt approach of entirely resetting a patient’s microbiome with a healthy one. Biotech companies are working to develop standardized, pre-screened fecal matter as a therapeutic for vancomycin-resistant C. difficiles infection –“unfriendly” bacteria that cause severe diarrhea, affecting several million people annually and leading to thousands of deaths. Other companies are working on a more targeted approach: defining specific bacterial strains or clearly defined communities of strains (consortia) of bacteria that are likely to be beneficial in a particular disease state, and isolating and developing these as a standardized therapeutic. This approach enables greater specificity and quality control. An even more targeted approach is to isolate a protein or small molecule being secreted by a strain of bacteria that gives it its therapeutic effect, and develop only that molecule as the therapeutic.Although this approach may be more in line with familiar development and approval pathways, in some cases these products may not be sufficient in treating microbiome-associated diseases, since drugs produced in this way will lack the ability to colonize the intestinal tract as an actual bacterium would. Further, there may be important and as-yet undefined interactions happening between different communities of bacteria that a single protein will not be able to replicate.