Latest news with #Cas9
Indian Express
27-05-2025
- Health
- Indian Express
Explained: A first— how a customised gene-editing tool was used to treat 9-month-old boy
A nine-month-old boy, born with a rare genetic disorder, has become the first (known) person to successfully receive a custom gene-editing treatment, a report published on May 15 in the New England Journal of Medicine said. Kyle 'KJ' Muldoon Jr suffers from CPS1 deficiency which causes toxic levels of ammonia to accumulate in his blood. To treat him, scientists and doctors from the University of Pennsylvania and the Children's Hospital of Philadelphia developed a personalised treatment based on 'base editing', a new version of the decade-old CRISPR-Cas9 technology. Scientists say this technology can potentially treat thousands of uncommon genetic diseases. But there remain many roadblocks to its universal adoption. What is CRISPR? Following infection by a virus, humans generate an 'immune memory' in the form of antibodies. When they are infected by the same virus again, these antibodies quickly identify the pathogens and help neutralise them. CRISPR, short for 'clustered regularly interspaced short palindromic repeats', is an immune system found in microbes such as bacteria which fights invading viruses. When a virus infects a bacterial cell, CRISPR too helps establish a memory — but a genetic one, not in the form of antibodies like in humans. When a virus enters a bacterial cell, the bacterium takes a piece of the virus's genome and inserts the DNA into its own genome. CRISPR then produces a new 'guide' RNA with the help of the newly acquired DNA. During a future attack by the same virus, the guide RNA quickly recognises the virus DNA and attaches itself to it. Then, the guide RNA directs an enzyme (a type of protein) called Cas9 to act like 'molecular scissors' to cut and eliminate the virus DNA. In 2012, scientists Jennifer Doudna and Emmanuelle Charpentier replicated this mechanism found in microbes to develop a gene-editing tool, which they called CRISPR-Cas9, a feat which earned them the Nobel Prize for Chemistry eight years later. How does CRISPR-Cas9 gene-editing work? The tool works much like the 'cut-copy-paste', or 'find-replace' functionalities in common computer programmes. Genetic information in DNA is stored as code made up of four chemical bases — adenine (A), guanine (G), cytosine (C), and thymine (T). These bases exist in pairs, which are then stacked one on top of each other, creating the horizontal layers of the double-helix structure of DNA. Note that A always pairs with T, and C always pairs with G. Genetic disorders, like the one KJ suffers from, occur due to the presence of an abnormal DNA sequence, that is, a mispairing (A-G or G-T). The first task for the gene-editing tool is to identify the abnormal DNA sequence behind a patient's ailment. Once the bad DNA is located, scientists create a guide RNA attached to a Cas9 enzyme, which is then introduced to the target cells of the patient. The guide RNA recognises the bad DNA sequence, then the Cas9 enzyme cuts the DNA at the specified location in a process called a 'double-strand break' (since the cut is made on both strands of the DNA). This gets rid of the DNA sequence causing the illness. DNA strands have a natural tendency to reattach and repair themselves, meaning there is a chance that the bad sequence regrows. To tackle this issue, scientists also supply the correct DNA sequence after the 'cutting' process which is meant to attach itself to the broken strands of DNA. Over the years, scientists have made many improvements to the original CRISPR-Cas9 technology, making it safer and more precise. A newer, evolved version of this tool is 'base editing'. How does base editing work? Base editing and CRISPR-Cas9 differ significantly in how they modify DNA. Unlike CRISPR-Cas9, base editing does not make a double-strand break. Rather, it enables targeted single-base conversions with the help of a Cas9 enzyme fused to a base-modifying enzyme. This allows scientists to fix mispairing of the bases by changing one specific base. For instance, mispaired A-C bases can be corrected to A-T by converting C to T. To treat KJ, scientists first determined which mispaired base in his DNA was causing his condition. They then programmed the base editing tool to find and rewrite the target base. This process can be likened to using a pencil and an eraser, rather than scissors and glue, as in CRISPR-Cas9. 'In the older version of CRISPR, scientists were required to provide additional DNA from outside, which would be pasted at the site where the double-strand break takes place. In base editing, however, the system by itself can make a very precise change without the need for a foreign DNA to be inserted,' Debojyoti Chakraborty, principal scientist at CSIR-Institute of Genomics and Integrative Biology, told The Indian Express. 'As a result, base editing has fewer components and is compact, making it easier to package in delivery vehicles, which can take it to target cells,' he said. In 2023, Chakraborty and his team tried to develop a similar tool to treat a patient with a rare neurodegenerative disease. But she passed away before the experiment could be carried out. Will base editing become commonplace soon? Chakraborty said the successful use of base editing for treating KJ has given hope to doctors treating people with rare genetic disorders for whom no medical treatments were currently available. However, it is unlikely that such technologies will become commonplace any time soon, first and foremost due to the prohibitive costs of such treatments. Even if it were to become widely available, base editing would not be accessible to most people. (KJ's treatment was funded by research institutes and biotechnology. While they did not make any official disclosure regarding its cost, it is likely to be in the range of hundreds of thousand dollars, maybe more). Also, the base editing tool created to help KJ was a one-off treatment, meaning it was designed specifically for his unique genetic disorder and cannot be used to treat other individuals with different disorders. This poses a unique challenge with regards to scaling up such technologies for mass consumption, something that disincentives pharmaceutical companies to invest in their development. Getting regulatory approvals is another issue. 'To do such a thing in India is very difficult because it also means that you will have to get rid of red tapism,' Chakraborty said. It remains to be seen how researchers make such personalised treatments more accessible. Till then, only a few fortunate people like KJ will benefit from base editing therapies.
CNBC
06-05-2025
- Health
- CNBC
CRISPR-based gene editing revolutionized medicine—what's next for the firm that helped develop it?
CRISPR-Cas 9 is a gene-editing tool that made it possible to rewrite any organism's genetic code and tackle genetic diseases more effectively. Known as genetic scissors, CRISPR identifies a DNA sequence that is cut by an enzyme called Cas 9. It then changes or replaces that sequence with a different section of DNA. For this discovery, co-inventors Emmanuelle Charpentier and Jennifer Doudna received the Nobel Prize in Chemistry in 2020. "By our interest in the lab to find new molecules that could have a role in in the bacterium streptococcus pardonus , we came across a very neat mechanism that allows to really recognize the virus that infects the bacterium in a very, very specific minor at the level of the genome of the virus. And we exploited this natural mechanism to develop the CRISPR-Cas9 technology," Emmanuelle Charpentier said in an interview with CNBC's The Edge. In 2013, Charpentier co-founded CRISPR Therapeutics to fulfil her lifelong goal of finding cures for diseases. A decade later, the company and its partner Vertex Pharmaceuticals developed CASGEVY, a therapy to treat blood disorders beta thalassemia and sickle cell disease. "With CASGEVY, we're taking the bone marrow cells from the patient, making the edit for that particular patient and we're putting it back into the patient, and it reconstitutes the hematopoietic system of the patient. We're making a drug just for you," CRISPR Therapeutics' CEO Samarth Kulkarni told The Edge. CASGEVY is a one-time therapy that costs $2.2 million per patient and can be administrated on patients 12 years of age and older. In 2023, it became the first CRISPR-based gene editing therapy to be approved by the Federal Drug Administration. CRISPR Therapeutics currently has seven clinical and ten pre-clinical programs across oncology, autoimmune cardiovascular disease and diabetes, and is investigating next generation editing modalities. Watch the video above for the full interview with Professor Charpentier from Berlin, Germany, and a tour of CRISPR Therapeutics' facilities in Boston, Massachusetts.
Associated Press
29-04-2025
- Business
- Associated Press
Biomay Obtains FDA Approval for Manufacturing of Cas9 Nuclease at Headquarters Site
The company announced its successful approval by the U.S. Food and Drug Administration (FDA) for the manufacturing, testing and release of recombinant Cas9 nuclease from its headquarters site. Cas9 is an essential component of CRISPR-based gene editing therapies, including CASGEVY® (exagamglogene autotemcel) developed and launched by Vertex Pharmaceuticals. Biomay's recent achievement refers to an inspection by the FDA's Center for Biologics Evaluation and Research (CBER) at Biomay's headquarters manufacturing site in Vienna, Seestadt in December 2024. No observation was found, and no Form FDA 483 was issued by the authority, allowing Biomay's headquarters site to supply Cas9 for the United States. Biomay operates two independent cGMP manufacturing sites, a headquarters facility in Vienna Seestadt, and a second site in Vienna downtown. The authority's approval of Biomay's headquarters site represents the company's second successful FDA inspection following the 2023 approval of Biomay's downtown facility. Biomay's headquarters site is a recently constructed, state-of-the-art biomanufacturing facility. Biomay AG is a privately owned and fully integrated Contract Development and Manufacturing Organization (CDMO) based in Vienna, Austria. Founded in 1984, the expression of recombinant proteins by utilizing E. coli has been Biomay's business focus from the very beginning. Today, Biomay offers cGMP services for manufacturing of therapeutic proteins, plasmid DNA (pDNA) and messenger RNA (mRNA). The company's scope of CDMO services comprises process and analytical development, cell banking, cGMP manufacturing of drug substance and aseptic filling of drug product.
Al Etihad
28-03-2025
- Health
- Al Etihad
DoH introduces advanced gene-editing therapy for sickle cell disease and thalassemia
28 Mar 2025 15:34 ABU DHABI (ALETIHAD)The Department of Health – Abu Dhabi (DoH) has announced the introduction of CASGEVY, the first CRISPR/Cas9 gene-editing therapy in the UAE, offering innovative treatment for patients suffering from sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT).The innovative treatment, provided by Abu Dhabi Stem Cells Center (ADSCC), in coordination with DoH and in collaboration with Vertex Pharmaceuticals, a leading biotechnology company, positions Abu Dhabi as a leading destination for life sciences. The first patient is scheduled to begin the groundbreaking therapy at Yas Clinic Hospital in April of this gene-editing is an innovative technology that enables precise genome editing to treat certain genetic diseases by targeting and altering specific DNA sequences. CASGEVY is a one-time treatment tailored for each patient by extracting the patient's own hematopoietic stem cells, genetically editing them in the lab, and then re-implanting them into the patient's body to provide long-term positive line with DoH's commitment to fostering innovation and ensuring the health and safety of patients in the emirate, the department has established regulations and guidelines for the management of gene therapies, according to the highest international standards. The treatment has been included in insurance coverage in accordance with established regulations and on the innovative treatment, Dr. Noura Khamis Al Ghaithi, Undersecretary, DoH, said: 'The Department of Health – Abu Dhabi remains dedicated to safeguarding the health and well-being of our community while continuously enhancing the quality of care. Our goal is to establish the world's most efficient healthcare system through the adoption of the latest innovations and promising technologies. By harnessing genomic sciences, we aim to develop cutting-edge therapeutic solutions to complex health challenges, solidifying Abu Dhabi's position as a global leader in healthcare, life sciences, and innovation.'For her part, Dr. Maysoon Al Karam, Chief Medical Officer at ADSCC and Yas Clinic, said: "Partnerships with leading biotechnology companies such as Vertex Pharmaceuticals represent a significant milestone in ADSCC's global mission, aligning with the UAE's vision and strategic health priorities. She explained, "Patients with genetic disorders such as thalassemia and sickle cell disease will greatly benefit from this revolutionary treatment, which we aim to offer as one of the first advanced gene therapies in the country. As the UAE's leading cellular research institution and the UAE's first FACT-accredited center, we strive through such partnerships to drive medical innovation, developing treatments for a range of critical diseases, and reinforcing Abu Dhabi's position as a global hub for life sciences, in line with the UAE's leadership Hagar, Senior Country Manager at Vertex GCC, said: 'We are delighted to partner with the Abu Dhabi Stem Cells Center, the UAE's leading cellular research institution, to bring the world's first CRISPR/Cas9 gene-editing medicine to patients in the UAE. This partnership represents a significant step toward bringing transformative medicines to patients in the UAE for serious diseases like SCD and TDT, ultimately advancing our mission to improve patients' lives in the UAE.' The Emirates Drug Establishment (EDE) in the UAE, has granted a market authorisation for CASGEVY to treat patients aged 12 years and older who suffer from sickle cell disease with recurrent vaso-occlusive crises, as well as transfusion-dependent thalassemia. Source: Aletihad - Abu Dhabi
