The 50 families stretch from the Netherlands and the United Kingdom to the United States and China. Each family has a child who is paralyzed from a mutation in a single gene named Contactin-Associated Protein 1 (Cntnap1).
The children are locked inside their bodies, unable to move. The families feed them and change them, and someone monitors them 24/7.
Thousands of miles away in South Texas, Manzoor Bhat, MS, Ph.D., and his team at The University of Texas Health Science Center at San Antonio are making discoveries that point to a gene therapy for these profoundly affected children. The journal Cell Reports published the findings. Co-authors of the study are Cheng Chang, Lacey Sell and Qian Shi, Ph.D.
"We obtained genetic information from the families and created mouse models that recapitulated the human mutations and the human disease. Our mice developed phenotypes, or weaknesses, like the children," said Bhat, vice dean for research in the health science center's Joe R. and Teresa Lozano Long School of Medicine.
Casgevy: UK approves gene-editing drug for sickle cell
15th November 2023, 10:30 PST
In a world first, medical regulators in the UK have approved a gene therapy that aims to cure two blood disorders.
The treatment for sickle cell disease and beta thalassemia is the first to be licensed using the gene-editing tool known as Crispr, for which its discoverers were awarded the Nobel prize in 2020.
This is a revolutionary advance for two inherited blood conditions, both triggered by errors in the gene for haemoglobin.
People with sickle cell disease produce unusually shaped red blood cells that can cause problems because they do not live as long as healthy blood cells and can block blood vessels, causing pain and life-threatening infections.
People with beta thalassaemia do not produce enough haemoglobin, which is used by red blood cells to carry oxygen around the body. Patients with beta thalassemia often need a blood transfusion every few weeks of their lives.
Microbial sequence databases contain a wealth of information about enzymes and other molecules that could be adapted for biotechnology. But these databases have grown so large in recent years that they've become difficult to search efficiently for enzymes of interest.
Now, scientists at the Broad Institute of MIT and Harvard, the McGovern Institute for Brain Research at MIT, and the National Center for Biotechnology Information (NCBI) at the National Institutes of Health have developed a new search algorithm that has identified 188 kinds of new rare CRISPR systems in bacterial genomes, encompassing thousands of individual systems. The work appears in Science.
The algorithm, which comes from the lab of CRISPR pioneer Feng Zhang, uses big-data clustering approaches to rapidly search massive amounts of genomic data. The team used their algorithm, called Fast Locality-Sensitive Hashing-based clustering (FLSHclust) to mine three major public databases that contain data from a wide range of unusual bacteria, including ones found in coal mines, breweries, Antarctic lakes, and dog saliva.
The scientists found a surprising number and diversity of CRISPR systems, including ones that could make edits to DNA in human cells, others that can target RNA, and many with a variety of other functions.
CRISPR systems are powerful tools for genetic engineering, but they have their limitations. Now, scientists have discovered almost 200 new CRISPR systems in their native habitat of bacteria, and found that some can edit human cells even more precisely than existing ones.
The CRISPR-Cas9 gene-editing tool is one of the most important scientific developments of the past decade, earning its discoverers a Nobel Prize in Chemistry. Scientists can use it to make efficient cut-and-paste edits to human cells, potentially treating a huge range of diseases, as well as improving crops, controlling pests, and manipulating bacteria.
The system contains a guide RNA that targets a segment of DNA, such as one that causes disease, then uses an enzyme, usually Cas9, to snip out that sequence and replace it with something more beneficial. More recently, alternatives to Cas9 have been developed with other properties, including higher precision or larger edits.
'One-and-Done' CRISPR Cholesterol Therapy Proves Cautiously Effective
A two-out-of-10 'serious adverse event' rate is concerning, to say the least.
By Adrianna Nine November 29, 2023
https://www.extremetech.com/science/one ... -effective
Verve Therapeutics, a Boston-based biotechnology firm, is on a mission to tackle cholesterol. One of its strategies involves editing the genes of those with high cholesterol, enabling their bodies to limit how much “bad” cholesterol forms in their blood. In a recent trial, Verve tested the viability of deactivating one cholesterol-regulating gene to produce long-term health effects. The therapy technically worked, but an alarming post-trial mortality rate now has the startup in hot water.
The human body can produce two types of cholesterol: high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. While HDL is often referred to as “good cholesterol” in that it helps the liver flush plaque out of the body, LDL is considered “bad cholesterol” for its tendency to form said plaque. As cardiovascular plaque is strongly associated with heart disease and cardiac arrest, some pills and injectables aim to reduce the amount of plaque in the bloodstream—but their side effects and cost make them more of a last resort than a go-to form of treatment. Contrary to popular belief, carefully controlling one’s diet only influences roughly 30% of one’s cholesterol levels.
Meet pAblo·pCasso: A new leap in CRISPR technologies for next-gen genome engineering https://phys.org/news/2024-01-pablopcas ... enome.html
by Danmarks Tekniske Universitet The Novo Nordisk Foundation Center for Biosustainability
A new CRISPR-Cas toolkit, dubbed "pAblo·pCasso," is set to transform the landscape of bacterial genome editing, offering unprecedented precision and flexibility in genetic engineering. The new technology, developed by researchers at The Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain), expands the range of genome sites available for base-editing and dramatically accelerates the development of bacteria for a wide range of bioproduction applications.
pAblo·pCasso sets a new standard in CRISPR-Cas technologies. A key innovation is to enable precise and reversible DNA edits within Gram-negative bacteria, a feat not achievable with previous CRISPR systems. The toolkit utilizes specialized fusion enzymes, modified Cas9 coupled with editor modules CBE or ABE, which act like molecular pencils to alter specific DNA nucleotides, thus accurately controlling gene function.
The development of pAblo·pCasso involved overcoming significant challenges. Traditional CRISPR-Cas systems were limited by their need for specific DNA sequences (PAM sequences) near the target site and were less effective in making precise, single-nucleotide changes. pAblo·pCasso transcends these limitations by incorporating advanced Cas-fusion variants that do not require specific PAM sequences, thereby expanding the range of possible genomic editing sites.
