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In Part 1 of this article series, we discussed how HIV infection and AIDS have become a major public health issue due to the ability of viral DNA to become part of human DNA. When this DNA is replicated, the infection spreads to other cells. This ends up developing into AIDS and suppressing the immune system, often to the point where the body is unable to fight off infection. The current treatment of HAART, which acts on various stages of the viral lifecycle to decrease the impact of HIV, is insufficient, so alternate treatments are being researched.

Researchers are actively studying the mystery of how the CRISPR/Cas system, a bacterial immune system, may be manipulated to treat HIV infection. CRISPR/Cas technology has paved the way for substantial changes in our ability to edit human genomes by tweaking the functioning of the immune systems of many types of bacteria. Some bacteria have the ability to remember viruses by copying short sequences, known as protospacers, from their genetic material. These copied sequences are integrated into the bacteria’s genetic material between repeating sequences. This produces a series of repeat sequences and integrated sequences within the host genome known as CRISPRs (clustered regularly interspaced short palindromic repeats), containing bacterial DNA and spacers constructed from viral DNA sequences.

A 3D model of Cas9, an endonuclease associated with CRISPR.

Image Source: Hao Jiang

Upon attack by a previously encountered virus, these spacers are transcribed into small CRISPR RNAs, proceeding to form a complex with CRISPR-associated (Cas) proteins. These small CRISPR RNAs guide these Cas proteins to the viral genetic material. The associated Cas molecules are known as endonucleases, which can cut in the middle of DNA molecules. In bacteria, these Cas molecules cleave protospacer sequences, allowing for the destruction of the viral DNA sequence. This allows for an effective immune response against familiar viruses.

Soon after the emergence of this research, several labs uncovered the potential for the CRISPR/Cas9 system to be used as a targeted endonuclease, spurring the creation of several new protocols to precisely cleave DNA. Essentially, these researchers figured out that by providing the Cas molecule with a specific RNA sequence, precise cuts could be made within the genome. They quickly adapted protocols to target the HIV virus by cutting out the viral DNA. In Part 3 of this article series, we will discuss these particular applications of CRISPR/Cas.

Feature Image Source: Lab Room by Heather Dowd

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