A few days ago we brought you the story of a new avenue for vaccine development, based on antibodies produced by about 20% of the HIV+ population. However, this isn’t the only way the human body can prevent HIV infection. A new study from a lab at the University of Pennsylvania has performed the first human trial of targeted gene editing to create genetically modified immune cells that are impervious to HIV, based off of an existing genetic mutation. The results were published in the New England Journal of Medicine.
The study focused on using a technique known as targeted gene editing to alter the conformation of C-C chemokine receptor type 5 (CCR5) delta32, which is a protein on the surface of T-cells that HIV uses to bind and infects the cell. If the protein is changed even slightly, the virus is not able to proceed. Though this cannot kill the virus, it does suppress the virus’s ability to proliferate, just like current medications taken by HIV patient, without the cost or nasty side effects.
A small portion of the global population carries an allele that cause this conformational change of CCR5-delta32 naturally, though a person would need to inherit a copy from each parent in order to have protection from HIV. Though as many as 14% of those with European ancestry may have the allele, it is rarely found in African or Asian populations, bringing the global total to about one percent. It is this mutation that served as inspiration for the study.
The trial itself had only twelve participants and was incredibly small; a fact the researchers acknowledge. However, two of them did not have sufficient T-cell counts to proceed with the research. Prior to the study which began in 2009, all of them took antiretroviral (ARV) medication as a standard treatment against the virus. After the T-cells had been collected, the researchers recreated the naturally-occurring CCR5-delta32 mutation and transfused the cells back into the patients. Not all of the cells took to the gene editing; only about one-fifth. After the newly-modified cells were transfused back in, their T-cell counts were tracked.
Over time, six patients showed a surge of resistance to the virus and actually stopped taking their daily ARV medications, though two of them would have to go back to them. Though the average immune cell lives for about six weeks, the modified cells could still be detected months later, and in a very interesting place: the gut. Recent research has indicated that HIV targets immune cells in the gut at the onset of infection.
It is important to note that these modifications have not eradicated the virus in the body; it has just made certain cells impervious to infection. Thus, even though a third of those participating in the study were able to stop taking daily medication, they are not cured; their body is just suppressing the virus as the pills would have.
Though it might not seem very noteworthy that a third of the participants from such a small study had good results, this research was the first of its kind. Information gathered here will be used to plan the next trial and the next, so on and so forth until it has been approved for clinical use to supplement, if not eliminate, the need to take expensive medications on a daily basis.