The team of Temple scientists who successfully eliminated HIV from human cells last July will seek to replicate their success in primates.
A team of researchers led by Dr. Kamel Khalili, director of the Comprehensive NeuroAIDS Center at the university and chair of the Department of Neuroscience, used newly emerging techniques in gene therapy and bioinformatics to arm immune system cells with highly targeted molecular “machinery” – also known the Cas9/gRNA system – that locates and eliminates HIV hiding inside human DNA.
“All the stars lined up for us,” Khalili said of the achievement first announced in July.
Once HIV infects the human body, it does not leave. Instead, it inserts itself into cellular DNA, wreaking havoc in the body’s immune system periodically. To date, dozens of available drug therapies can subdue the virus, but none can remove it from a cell.
“As long as [the cells] have Cas9 and there is a particular targeting RNA in the cell, cells become protected from HIV infections,” Khalili said.
The team “taught” the cells to “delete” HIV by inserting DNA-encoded instructions for the Cas9/gRNA machinery. The cells “read” the instructions and assemble a DNA-cutting enzyme (Cas9), and an HIV-specific tag (gRNA) which locates the virus inside the cell. Once the virus is eliminated, cells use their own enzymes to repair themselves.
The technology is not only specific, but also highly customizable. RNA tags can easily be tailored to capture HIV even if it mutates, said Dr. Wenhui Hu, who co-directed the study with Dr. Khalili.
So far, the team has successfully eliminated HIV from cell lines, but proving this concept in whole organisms poses new challenges.
“Our biggest challenge is to find a [safe and effective] delivery system [into the body],” said Dr. Rafal Kaminski, a member of the research team. “We don’t have control [over where] our [Cas9/gRNA] genes get integrated. This could be potentially unsafe if the segment disrupts working genes,“ he said.
Despite these potential difficulties, Khalili and his team believe their initial results can eventually be replicated in primates, and then in humans.
However, Khalili stressed that this discovery is far from ready for the clinic. The team is seeking funding sources to continue this line of research.
“We’re going to do our utmost to get this technology to patients as soon as possible,” he said.
And there are many patients who could benefit from this treatment. According to a 2012 CDC estimate, more than 1.2 million Americans aged 13 or older live with HIV. An additional 50,000 Americans are infected annually.
Meanwhile, the team has collaborated with University of Pennsylvania and Drexel scientists to combat with the same technology.
“We’re moving forward in the HIV eradication project, and we are also assisting other scientists at Temple and outside of Temple to implement this technology for their own research in other areas,” Khalili said.
Liora Engel-Smith can be reached at email@example.com