A human RNA (ribonucleic acid)-based gene therapy trial to combat HIV (human immunodeficiency virus) has passed the first safety test.
US researchers modified human blood stem cells to make them resistant to the virus. The cells were then transplanted into four AIDS patients and survived for up to two years without adverse effects.
The trial was based on an existing therapy for AIDS (acquired immune deficiency syndrome) patients, which involves the transplantation of a patients' own previously saved blood stem cells back into their bloodstream in an attempt to prevent the development of lymphoma, a type of blood cancer. This latest trial transplanted blood stem cells engineered to be HIV-resistant alongside the patient's normal blood stem cells.
The engineered blood cells were manipulated in three ways, each via RNA-based gene therapy, to make them HIV-resistant. First, the cells expressed an RNA enzyme that prevented the production of the protein CCR5. HIV exploits the presence of CCR5 on the surface of immune cells to gain entry. 'We know from a lot of populations that this is a great target - it can down-regulate (HIV levels) by 90 per cent', said Professor John Rossi of the Beckman Research Institute, California, who was involved in the trial.
The cells were also manipulated to express two types of RNA that both disrupt, in different ways, the HIV viral protein tat, which is essential for its replication. The transplanted, modified cells were shown to survive for between 18 and 24 months in three of the four patients involved in the study.
'It's a small study, but it's a step in the right direction. The most promising thing is that it shows you can modify stem cells in a way that makes them [HIV-] resistant, and the progeny of those cells would still be resistant to HIV and would still be functional', said Associate Professor Pablo Tebas, a HIV researcher at the University of Pennsylvania, who was not involved in the study.
'What we really want to do now is increase the percentage of gene-modified cells in the patient', said Professor Rossi. Professor Rossi and colleagues hope to achieve this goal in collaboration with the Australian biotechnology company Benitech.
The research was published in Science Translational Medicine this month.
