CRISPR Gene Editing for Sickle Cell and Beta-Thalassemia
In November 2023, the UK Medicines and Healthcare Products Regulatory Agency approved the world's first CRISPR gene-editing therapy for treating sickle cell disease and transfusion-dependent beta-thalassemia in patients 12 and older.
CRISPR-Cas: A Molecular Tool to Target HIV
On March 19, 2024, researchers from Amsterdam UMC in the Netherlands reported at a medical conference that they successfully eliminated all traces of HIV from infected cells using CRISPR gene-editing technology.
The researchers presented their findings at the European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024), which was scheduled to take place in Barcelona, Spain, from April 27 to 30, 2024.
The study was led by Dr. Elena Herrera-Carrillo and team members Yuan-Ling Bao, Zhenghao Yu, and Pascal Kroon from Amsterdam UMC.
CRISPR, an acronym for Clustered Regularly Interspaced Short Palindromic Repeats, is a natural bacterial defense mechanism that scientists have adapted for gene editing. French scientist Emmanuelle Charpentier and American scientist Jennifer Doudna received the 2020 Nobel Prize in Chemistry for their development of the technology, which allows for precise and efficient genome modification.
A major challenge in HIV treatment is that the virus integrates its genome into the host's DNA. While current antiretroviral medications can suppress HIV replication, they cannot eliminate the virus, requiring patients to remain on lifelong therapy. If treatment is stopped, HIV can rebound.
HIV infects different cell types and tissues with distinct environments and characteristics. According to the Dutch researchers, CRISPR-Cas acts like "molecular scissors" that cut DNA at specific locations guided by RNA molecules (gRNAs). "We are seeking to develop a powerful and safe combination of CRISPR-Cas systems that can eliminate diverse HIV strains in these different cellular environments," they stated.
CRISPR Targets Conserved Viral Sequences
In their study, the researchers used "molecular scissors" with two gRNAs that targeted conserved regions of the viral genome present in all known HIV strains and successfully cured infected T cells.
The researchers further evaluated different CRISPR-Cas systems from various bacteria and demonstrated the efficient performance of saCas9 and cjCas systems. saCas9 showed superior antiviral activity, completely inactivating HIV with a single gRNA and excising the viral DNA with two gRNAs.
The researchers demonstrated that their CRISPR systems, when tested in cultured immune cells, could eliminate all traces of HIV, effectively purging it from the immune cells.
Clinical Applications Remain a Distance
It's important to note that the Amsterdam UMC team emphasized at the medical conference that their work is still "proof-of-concept" and will not become a treatment for HIV anytime soon.
Dr. James Dickenson, Associate Professor in Stem Cells and Gene Therapy Technologies at the University of Nottingham in the UK, agreed, stating that the full study results need careful scrutiny. "More work is required to demonstrate that these laboratory-based findings can be replicated in whole organisms before such treatments can progress to human applications."
Other scientists are also exploring CRISPR for HIV. In October 2023, Excision BioTherapeutics, a US biotech company, reported that three HIV-positive volunteers showed no serious side effects after 48 weeks of CRISPR treatment.
However, Dr. Jonathan Stoye, a virologist at the Francis Crick Institute in London, said that while the Amsterdam UMC team's results were encouraging, the next step would be to test the approach in animal models and ultimately in humans to show that the treatment can reach all immune cells harboring latent HIV. Some of these cells are thought to reside in the bone marrow, but other body sites may also be involved, Stoye noted.
"Concerns remain about off-target effects of the treatment and the potential for long-term side effects," Stoye said. "So even if this CRISPR-based approach proves effective, it is likely to be many years before any such CRISPR-based treatments might become routine."
