Researchers received the go-ahead from the FDA to test a gene-editing technique in humans and produce a “functional cure” for HIV.
The trial at the City of Hope medical Center (CA, USA) aims to take blood-producing stem cells from patients infected with HIV and use zinc finger nucleases, a kind of “molecular scissors”, to edit a protein that the virus uses to infect cells. The method was developed by Richmond’s Sangamo BioSciences Inc (VA, USA).
The trial is not the first gene-editing technology to reach human clinical trials. For example, back in 2013 Calimmune (CA, USA) treated its first patient in a Phase I/II study using a different gene-editing method. However this technique is significant because it potentially could lead to a cure, rather than chronic treatment, for HIV.
By editing a protein called CCR5, City of Hope researchers believe the CCR5 gene that HIV uses to infect cells will be disabled. As a result, the offspring of the edited cells will continue to be resistant to the virus. The edited cells will be reintroduced into patients in order to create an immunological resistance against HIV.
This would also represent a major triumph for the California Institute for Regenerative Medicine, the state’s stem cell program, which provided $5.6 million to support City of Hope’s trial.
Researchers say the Sangamo approach is promising, but it remains to be seen how well these replacement stem cells will function. Gene editing technology has the potential for “off-target” effects if it also disrupts important genetic activity elsewhere and the altered stem cells must be examined to check for unintentional alterations.
Sangamo’s approach was inspired by certain rare patients who strongly resist HIV infection due to their mutated forms of the CD4+ immune cell which lack the CCR5 surface molecule HIV strains commonly infect. Knowing this, a HIV patient who also suffered from leukemia, the famous Berlin patient, was given a bone marrow transplant in 2007 to cure his leukemia with cells were taken from another person who had mutated CCR5, which could block HIV. The goal was to cure both the leukemia and the HIV with one treatment and his new immune system is now able to control HIV on its own, which is the result Sangamo wants to replicate in its clinical trials.
While this is a Phase I safety study, the FDA’s approval of the City of Hope’s investigational new drug application (IND) is a major step forward, commented Paul Knoepfler, stem cell researcher at the University of California, Davis.
“‘Cure’ is a big word, but there’s hope,” stated Paul Knoepfler. “First step is to assess safety, but IND approval is (a) major positive step. Then determine efficacy.”
1.San Francisco Business Times: http://www.bizjournals.com/sanfrancisco/blog/biotech/2015/03/hiv-aids-cirm-stem-cells-sangamo-sgmo-usc.html?ana=twt
2.The San Diego Union-Tribune: http://www.utsandiego.com/news/2015/mar/04/sangamo-hiv-cure-ccr5/2/?#article-copy
For more information:
– Clinical Data from Sangamo’s trial: http://www.prnewswire.com/news-releases/sangamo-biosciences-presents-new-clinical-data-at-croi-2015-from-trial-of-zfp-therapeutic-designed-to-provide-functional-control-of-hiv-300041880.html
– The Berlin Patient story: http://online.liebertpub.com/doi/full/10.1089/aid.2014.0224
– Free Editorial on “engineering HIV-1-resistant hematopoietic stem cells” from Dr HÃ¼tter, who treated the Berlin Patient: http://www.futuremedicine.com/toc/rme/9/6