CRISPR versus HIV

HIV infection affects more than 35 million people worldwide. Over the past three decades, progress has been made in HIV treatment, mostly through the use of antiretroviral drug therapies, yet there is no way HIV can be eradicated from infected cells….Or is there?

Scientists at several research institutions have now shown that genome editing technologies such as CRISPR/Cas may soon be used to treat HIV infection, maybe even completely erase it!

■ A group at Kyoto University, led by Yoshio Koyanagi showed that the CRISPR/Cas system can be used to edit an integrated HIV genome. They were able to suppress HIV gene expression by mutating the viral LTR and also used CRISPR/Cas to excise HIV provirus from host cells. (Ebina et al 2013)

■ At Temple University, KamelKhalili’s team took a similar approach, but first they identified specific target sites in the integrated HIV genome that can efficiently edited by CRISPR/Cas. They then targeted these sites to inactivate viral gene expression and replication in infected T-cells, microglia, and monocytic cells. They also showed that HIV infection can be prevented by stably expressing guide RNAs within Cas-expressing cells. (Hu et al 2014)

■ Around the same time, a group led by Derrick Rossi and Chad Cowanin Massachusetts used the CRISPR/Cas system to attack HIV in a different way. They collected primary human T-cells and hematopoietic stem cells (HSCs), and used CRISPR/Cas to target B2M and CCR5, two clinically relevant genes in HIV infection. They also showed that HSCs that have undergone genome editing retain their multilineage potential, which opens the door for hematopoietic cell-based therapies. (Mandal et al 2014)

■ Recently, Juan Carlos Izpisua Belmonte’s group at the Salk Institute adapted the CRISPR/Cas system to provide an intracellular defense against HIV infection. By inserting a stably expressed CRISPR/Cas system they were able to disrupt latent HIV and also give a cell line long-term resistance to HIV infection. (Liao et al 2015)

For more than 30 years, researchers have searched for ways to cure HIV. Now, with the power of genome editing technologies such as CRISPR/Cas, a cure may be possible.

What are you going to do with the power of genome editing?

Cyagen offers a complete line of genome editing services using TALENs and CRISPR/Cas. Visit Cyagen.com to learn about our rapid and cost-effective genome editing options for animal models, or visit VectorBuilder.com for custom TALEN and CRISPR/Cas vectors.

References

1. Ebina H, Misawa N, Kanemura Y, Koyanagi Y. (2013) Harnessing the CRISPR/Cas system to disrupt latent HIV-1 provirus. Scientific Reports,3:2510
2. Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F, Luo B, Alvarez-Carbonell D, Garcia-Mesa Y, Karn J, Mo X, Khalili K. (2014) RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. PNAS, 111:11461-6.
3. Mandal PK, Ferreira LM, Collins R, Meissner TB, Boutwell CL, Friesen M, Vrbanac V, Garrison BS, Stortchevoi A, Bryder D, Musunuru K, Brand H, Tager AM, Allen TM, Talkowski ME, Rossi DJ, Cowan CA. (2014) Efficient ablation of genes in human hematopoietic stem and effector cells using CRISPR/Cas.Cell Stem Cell, 15:643-52.
4. Liao HK, Gu Y, Diaz A, Marlett J, Takahashi Y, Li M, Suzuki K, Xu R, Hishida T, Chang CJ, Esteban CR, Young J, Izpisua Belmonte JC. (2015) Use of the CRISPR/Cas system as an intracellular defense against HIV-1 infection in human cells. Nature Communications, 6:6413