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At Oak Ridge National Laboratory (ORNL), quantum biology, artificial intelligence, and bioengineering have collided to redefine the landscape of CRISPR Cas9 genome editing tools. This multidisciplinary approach, detailed in the journal Nucleic Acids Research, promises to elevate the precision and efficiency of genetic modifications in organisms, particularly microbes, paving the way for enhanced production of renewable fuels and chemicals.

CRISPR is adept at modifying genetic code to enhance an organism’s performance or correct mutations. CRISPR Cas9 requires a guide RNA (gRNA) to direct the enzyme to its target site to perform these modifications. However, existing computational models for predicting effective guide RNAs in CRISPR tools have shown limited efficiency when applied to microbes. ORNL’s Synthetic Biology group, led by Carrie Eckert, observed these disparities and set out to bridge the gap.

“A lot of the CRISPR tools have been developed for mammalian cells, fruit flies, or other model species. Few have been geared towards microbes where the chromosomal structures and sizes are very different,” explained Eckert.

A pair of studies from the laboratory of Evangelos Kiskinis, Ph.D., associate professor in the Ken and Ruth Davee Department of Neurology’s Division of Neuromuscular Disease and of Neuroscience, have uncovered novel cellular mechanisms that are involved in two types of genetic amyotrophic lateral sclerosis, or ALS.

The findings, published in Science Advances and Cell Reports, improve the understanding of ALS, a progressive neurodegenerative disease that attacks motor neurons in the brain and spinal cord, and provides support for the future development of targeted therapies.

An estimated 32,000 individuals are currently living with ALS in the U.S., according to the Les Turner ALS Foundation. There are two types of ALS: sporadic (non-genetic), which makes up more than 90% of all ALS cases, and familial (genetic).

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Adoptive cell therapy has emerged as a promising alternative treatment for hematological and solid cancers, with CAR-T therapy standing out as a prominent avenue. In this approach, T cells are genetically engineered with chimeric antigen receptors (CARs) to enhance their targeting capabilities^1–2. The outcome of CAR-T cell therapy hinges on a complex interplay of phenotype, activation, and functional profiling of these engineered cells. Immunophenotypic characterization of CAR-T cells assumes a pivotal role in ensuring treatment quality and facilitating continuous monitoring of treatment response¹. In the process of immunophenotyping, engineered T cells are separated based on their markers to characterize the composition of the cell population within the sample. The strategic identification and isolation of specific CAR-T cell subsets is essential in augmenting therapy responses².

Deciphering Cellular Composition, Defining CAR-T Therapy Efficacy

Immunophenotyping is a pivotal technique that combines specific antibodies with fluorescent compounds to reveal specific protein expression in cell populations to identify categorize the tagged cells. Immunophenotyping leverages the differences in surface markers among T cells, reflecting their differentiation, activation, and memory status². These markers provide insights into immune cell development, function, proliferation potential, and long-term viability. The distinct surface marker profiles closely correlate with the efficacy of CAR-T cell therapy³. Essential markers for immunophenotypic analysis, including CD3, CD4, CD8, CD45RA, CD34R0, CCR7, CD27, and CD95, are presented in Table 1.

So they volunteered for an experimental cholesterol-lowering treatment using gene editing that was unlike anything tried in patients before.

The result, reported Sunday by the company Verve Therapeutics of Boston at a meeting of the American Heart Association, showed that the treatment appeared to reduce cholesterol levels markedly in patients and that it appeared to be safe.

The trial involved only 10 patients, with an average age of 54. Each had a genetic abnormality, familial hypercholesterolemia, that affects around one million people in the United States. But the findings could also point the way for millions of other patients around the world who are contending with heart disease, which remains a leading cause of death. In the United States alone, more than 800,000 people have heart attacks each year.

Oak Ridge National Laboratory’s research in quantum biology and AI has significantly improved the efficiency of CRISPR Cas9 genome editing in microbes, aiding in renewable energy development.

Scientists at Oak Ridge National Laboratory (ORNL) used their expertise in quantum biology, artificial intelligence, and bioengineering to improve how CRISPR Cas9 genome editing tools work on organisms like microbes that can be modified to produce renewable fuels and chemicals.

CRISPR is a powerful tool for bioengineering, used to modify genetic code to improve an organism’s performance or to correct mutations. The CRISPR Cas9 tool relies on a single, unique guide RNA.

Treating mental disorders with fewer side effects

Now, researchers have managed to genetically modify yeast cells to produce drugs for mental disorders such as schizophrenia with fewer side effects.

“Development of medicines from natural plant substances is widely used. However, since plants do not produce these substances to fight human diseases, there is often a need to modify them to make them more effective and safe,” said Michael Krogh Jensen, a senior researcher at DTU Biosustain and co-founder of the biotech company Biomia.

Only 2% of Alzheimer’s is 100% genetic. The rest is up to your daily habits.

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