Stories of Discovery: Professor David Schaffer
Human Immunodeficiency Virus (HIV) is one of the most destructive pandemics in human history. According to WHO estimates, 33.2 million people were living with HIV at the end of 2007. The virus has caused an estimated 25 million deaths since 1981, and left millions of orphans. Two thirds of infections are in sub-Saharan Africa, with adult prevalence reaching as high as 26% in Swaziland.
David Schaffer, CEND investigator and UC Berkeley professor, has discovered a potentially life-saving new way to combat HIV using synthetic biology, resolving some of the issues with current HIV treatments. Professor Schaffer, along with fellow CEND investigator Adam Arkin and graduate student Leor Weinberger, has created a virus that uses HIV as a host, preventing the onset of AIDS. Although still in development, Schaffer’s “parasite of a parasite” could eventually end the spread of one of the world’s most destructive viruses.
HIV attacks CD4+ T cells and macrophages, specialized white blood cells that are vital to the immune system. Once inside, the virus uses the cells’ machinery to replicate. As the infection spreads, the body’s immune system deteriorates (the phenomenon after which the virus is named), eventually resulting in acquired immunodeficiency syndrome (AIDS). The weakened immune system causes individuals with AIDS to be susceptible to numerous cancers, as well as a host of viral, bacterial, and fungal infections that are not typically seen in a healthy population. It’s these opportunistic infections (such as Tuberculosis and pneumonia) which ultimately kill them, not the virus itself.
Anti-retroviral (ARV) treatments have been developed to effectively delay the onset of AIDS after HIV infection, and have extended the life expectancy of people living with HIV. However, there are critical problems with ARVs. First, the treatment remains prohibitively expensive. Many of the HIV positive people who would benefit from ARV treatment live in resource-poor regions of the world, with little or no savings, and no provisions for healthcare. They simply can’t afford the potentially life-saving treatment. Second, the treatments are highly toxic, and can cause severe side-effects in users, including nerve damage and death. This is a particular concern for patients who are receiving simultaneous treatment for other infections. Multi-drug therapies can have so-called “overlapping toxicities,” in which the negative side-effects of one drug are amplified by the addition of other treatments, leading many to discontinue use. Finally, because these are drugs that must be taken everyday of one’s life, non-compliance is problematic. If the patient misses a dose, or does not take the correct pills at the correct time, then the treatment could be rendered ineffective, and the virus can gain resistance. Despite the vast improvements in health and life-expectancy that ARVs have brought, expense, non-compliance, and severe side-effects remain significant barriers, particularly for the severely impoverished populations that are most burdened by the virus.
Professor Schaffer and his team have created an alternative to the problematic ARV treatments. They used computer modeling to simulate an HIV attack on the immune system, and then designed a virus to interfere with the process. Much like ARVs, which block key replicating agents within HIV, the cargo inside the synthetic virus is designed to latch onto the key parts of the natural virus’s genetic material, inhibiting its ability to reproduce and destroy immune cells. The difference is that this treatment is not a drug regimen, but essentially another infection. The treatment would remain with the patient as long as he or she is infected with HIV, and would additionally spread along with the natural infection.
Although an actual treatment is still years away, Schaffer’s “parasite of a parasite” approach to finding a cure for HIV is an exciting new paradigm.
