文摘
The battle with human immunodeficiency virus (HIV) has been ongoing for more than 30 years, and although progress has been made, there are still significant challenges remaining. A few unique features render HIV to be one of the toughest viruses to conquer in the modern medicine era, such as the ability to target the host immune system, persist by integrating into the host genome and adapt to a hostile environment such as a single anti-HIV medication by continuously evolving. The finding of combination anti-retroviral therapy (cART) about 2 decades ago has transformed the treatment options for HIV-infected patients and significantly improved patient outcomes. However, finding an HIV cure has proven to be extremely challenging with the only known exception being the so-called “Berlin patient,” whose immune system was replaced by stem cell transplants from a donor missing one of HIV's key co-receptors (CCR5). The broad application of this approach is limited by the requirement of an HLA-matched donor who is also homozygous for the rare CCR5 delta32 deletion. On the other hand, the Berlin patient provided the proof of concept of a potential cure for HIV using HIV-resistant hematopoietic stem cells (HSCs), revitalizing the hope to find an HIV cure that is broadly applicable. Here we will review strategies and recent attempts to engineer HIV-resistant HSCs as a path to an HIV cure.