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CRISPR System Provide Immunity & Raise Hopes for a Better Cure for AIDS
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CRISPR System Provide Immunity & Raise Hopes for a Better Cure for AIDS

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Highlights:
  • HIV is a dreaded virus that leads to the development of AIDS. Some people are immune to HIV infection.
  • HIV hides in certain genes that aid in avoiding drug therapy.
  • Current study identifies that mutation in CXCR4/CCR4 leads to immunity against HIV.
  • CRISPR/CAS9 system used to edit genes in T-cells to induce immunity.

The Human immunodeficiency virus (HIV) affects the T cells in the body and prevents them from mounting a response. A few individuals are found to be resistant to HIV infection and such individuals were studied by researchers from The University of California San Francisco to identify the mutations that gave rise to the immunity. The new gene editing tool CRISPR/cas9 system was used to edit the specific gene elements to determine if it leads to immunity against the virus.

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HIV Infection
  • HIV infection has affected 78 million people
  • 35 million people are believed to have died due to the disease
  • In 2015, 38.7 million people were found to live with HIV
  • 1.8 million were children.
  • In the same year 1.1 million died of the illness.
The infection is dreaded across the world as it is sexually transmitted with limited medical support. The virus gets into the DNA of the immune cells and is difficult to remove from the system with the currently available medication. This necessitates life-long medication.

Some individuals host an immune response that prevents the growth and multiplication of HIV, this lead the researchers in the current study to identify the genetic pattern of these HIV resistant individuals.
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One of the lead authors of the study, Judd F. Hultquist said "There have been lots of efforts to sequence the genomes of resistant people to discover the mutations that make them immune to the virus. But there are many different genes that could be involved: some control the virus's ability to enter immune cells, others control how the virus tricks cells into expressing its genes. Until now, there was no way to test which of these mutations actually confer resistance in primary human T-cells."

DNA Replacement using CRISPR

The human T cells survive for a very short time out of the human body and hence, any study that needs to be carried out on the T-cells has to be immediate. The use of viruses in earlier studies to create changes to the DNA proved futile when immune cells were involved.

In the current study, the research team was able to produce changes to the immune cell DNA using the CRISPR/Cas 9 system.

The specially designed CRISPR/Cas 9 system were added to immune cells that were freshly harvested and the gene editing tool made the appropriate changes after which it underwent cellular degradation before it could make any further changes to the immune cell DNA.

Identifying DNA Mutations Using High Throughput Parallel T cell Editing System

The researchers in the study used high throughput T-cell DNA editing system where candidate genes at different positions in the T cell DNA of many T-cells were carried out in parallel. These T-cells were then exposed to HIV to identify which mutation rendered the cell immune to the virus.

This new technique increased the speed as many DNA mutations could be carried out within a short period of time, which is highly critical as T-cells last only for a short while outside the body. If this technique needs to be tailored for a cure, carrying out the DNA mutation within a short period of time will form the crux of the treatment as the DNA of the T cells need to be altered and then injected into the patient within a short period of time.

Genes Identified

The researchers identified two genes CXCR4 and CCR4 into which the HIV 'hid' during an infection. When these two genes were mutated, the cells were immune to the virus.

This study on the infectivity of HIV and the resultant immunity in certain T cells could lead to better treatment for HIV.

Highlights of the Study:
  • The study found that mutations in the genes CXCR4 and CCR4 were found to provide immunity against HIV infection.
  • CRISPR/Cas 9 system was used to edit the genes of freshly harvested immune cells of susceptible individuals.
  • The processes of editing and reintroduction into the host were completed within a short span of time, a first of its kind and of high relevance as T-cells survive for a very short time outside the body.
  • Promises better method of treatment as well as prophylaxis against HIV.
Reference :
  1. Global HIV and AIDS statistics - (http://www.avert.org/global-hiv-and-aids-statistics)
Source: Medindia

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