Abstract:
Current treatment for HIV-1 largely relies on chemotherapy through the administration of antiretroviral drugs. While
the search for anti-HIV-1 vaccine remain elusive, the use of highly active antiretroviral therapies (HAART) have been
far-reaching and has changed HIV-1 into a manageable chronic infection. There is compelling evidence, including sev‑
eral side-effects of ARTs, suggesting that eradication of HIV-1 cannot depend solely on antiretrovirals. Gene therapy,
an expanding treatment strategy, using RNA interference (RNAi) and programmable nucleases such as meganuclease,
zinc finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN), and clustered regularly interspaced
short palindromic repeats/CRISPR-associated proteins (CRISPR–Cas9) are transforming the therapeutic landscape
of HIV-1. TALENS and ZFNS are structurally similar modular systems, which consist of a FokI endonuclease fused to
custom-designed effector proteins but have been largely limited, particularly ZFNs, due to their complexity and cost
of protein engineering. However, the newly developed CRISPR–Cas9 system, consists of a single guide RNA (sgRNA),
which directs a Cas9 endonuclease to complementary target sites, and serves as a superior alternative to the previous
protein-based systems. The techniques have been successfully applied to the development of better HIV-1 models,
generation of protective mutations in endogenous/host cells, disruption of HIV-1 genomes and even reactivating
latent viruses for better detection and clearance by host immune response. Here, we focus on gene editing-based
HIV-1 treatment and research in addition to providing perspectives for refining these techniques.
