CAN HIV BE CURED BY GENE THERAPY? Jiayi (Ariel) Cao, LVI
The World Health Organisation had estimated that around 680,000 people had died due to HIV-related illness in 2020 (WHO, 2020). Although numbers are declining, HIV is still responsible for over half a million deaths across the globe. Over the course of medical and scientific advancement, there has been developmental drug treatments and post-exposure prophylaxis, but the battle against HIV has not stopped as there is still no cure.
REFERENCES Excision BioTheraputics. (2021). Excision Receives FDA Clearance of IND for Phase 1/2 Trial of EBT-101 CRISPRBased Therapeutic for Treatment of HIV. Joanna Smolen-Dzirba, e. a. (2017). V-1 Infection in Persons Homozygous for CCR5-delta 32 Allele: The Next Case and the Review. Qiaoqiao Xiao, e. a. (2019). Application of CRISPR/Cas9-Based Gene Editing in HIV-1/ AIDS Therapy. WHO. (2020).
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NATURAL IMMUNITY
BERLIN PATIENT
Contrasting the turmoil of HIV patients, around 10% of Europeans are naturally resistant to HIV infection. The consensus is that this is caused by a mutation in the gene that codes for the membrane protein receptor (CCR5) that HIV virus binds to to enter and infect human immune cells, which prevents the entry of HIV by taking away the ‘door handle’ to HIV’s target cells.
Timothy Ray Brown (often referred to as the Berlin Patient) had been diagnosed with acute myeloid leukaemia and tested positive for HIV infection. He was the first person on this planet to be cured of HIV after receiving a stem cell transplant (which is also a treatment for his leukaemia) from a donor who possessed homozygous CCR5-Δ32. Although this is the first and currently only case of successful cure for HIV using stem cell transplantation, this idea can be considered when treating all HIV patients. Could we artificially induce this gene into HIV patients to induce immunity? The answer is that scientists are working on it.
More specifically, HIV virus binds to the CD4 receptor of the target cell along with either CCR5 or CXCR4 membrane coreceptor depending on the viral strain. The HIV-1 R5 strains, which cause most HIV infections, binds to the CCR5 molecule (C-C chemokine receptor 5) on the host cell membrane. Among the lucky 10% of Europeans, they carry a genetic mutation termed CCR5-Δ32, which means a frame-shifting deletion of 32 nucleotides in the DNA sequence that codes for the protein CCR5. This mutation changes the shape of the CCR5 receptor and prevents it from presenting on the outside of the cell, which impedes the binding of HIV on the membrane receptor and consequently blocks the entry of HIV into the immune cell. Recent studies have shown that although homozygous CCR5-Δ32 is highly protective against HIV-1 R5, heterozygous CCR5-Δ32 has no effect on HIV immunity but is still related to the delayed progression of AIDS. (Joanna SmolenDzirba, 2017)
CRISPR-BASED GENE THERAPY The 2020 Nobel Prize in Chemistry was awarded to scientists who pioneered the genetic engineering technique CRISPR/cas9, which has proven to be one of the most effective techniques in gene editing. This provides potential opportunities to edit the CCR5 gene in HIV patients to intentionally induce CCR5-Δ32 and thus HIV immunity. In lab research conducted by Xiaoqiao Xiao, et al., an application of gene editing to inhibit HIV infection had been successful in vitro and in mouse models, which could potentially be performed on HIV patients to induce HIV immunity or even HIV prevention. (Qiaoqiao Xiao, 2019)
