An Assessment of HIV Treatment Using CCR5 Targeted Cell Therapy and Preventing Viral Escape

Abstract In an HIV-positive person in 2008, allogeneic transplantation using homozygous CCR5-delta 32 (CCR5-d32) stem cells resulted in long-term viral control and likely HIV eradication. Since then, there has been a lot of interest in expanding the use of this strategy. There are two methods for doing this in cells. The first is to replicate the original discovery using a CCR5 negative cell source, such as hematopoietic stem cells (HSC). On the other hand, viral escape of CXCR4 quasi-species was seen in a recent example of a second allogeneic transplantation using homozygous stem cells expressing CCR5-d32. The second method involves using gene therapy to reduce CCR5 expression. There are now five procedures that show promise, three of which are undergoing clinical trials. Short hairpin RNA (shRNA), zinc finger nucleases (ZFN), transcription activator-like effectors nuclease (TALEN), clustered regularly interspaced palindromic repeats/CRISPR-associated protein 9 nuclease (CRISPR/Cas9), and a ribozyme are some of these methods. While many other gene therapy approaches are being investigated, in this review we focus on what we now know about the particular suppression of CCR5 and whether or not this allows for subsequent viral escape. Keywords: HIV-1; CCR5; CCR5 delta-2; tropism; genetherapy; viral escape; chemokine receptor, etc,.