Lifeboat Foundation

In the latest of ongoing efforts to expand technologies for modifying genes and their expression, researchers have developed chemically modified guide RNAs for a CRISPR system that targets RNA instead of DNA. These chemically-modified guide RNAs significantly enhance the ability to target — trace, edit, and/or knockdown — RNA in human cells.

In a study published today in Cell Chemical Biology, the team explores a range of different RNA modifications and details how the modified guides increase efficiencies of CRISPR activity from 2-to 5-fold over unmodified guides. They also show that the optimized chemical modifications extend CRISPR targeting activity from 48 hours to four days. The researchers worked in collaboration with scientists at Synthego Corporation and New England BioLabs, bringing together a diverse team with expertise in enzyme purification and RNA chemistry. To apply these optimized chemical modifications, the research team targeted cell surface receptors in human T cells from healthy donors and a “universal” segment of the genetic sequence shared by all known variants of the RNA virus SARS-COV-2, which is responsible for the COVID-19 pandemic.

Increasing the efficiencies and “life” of CRISPR-Cas13 guides is of critical value to researchers and drug developers, allowing for better gene knockdown and more time to study how the gene influences other genes in related pathways.

“CRISPR RNA guide delivery can be challenging, with knockdown time limited due to rapid guide degradation. We were inspired by the guide modifications developed for other DNA-targeting CRISPRs and wanted to test if chemically modified guides could improve knockdown time for RNA-targeting CRISPR-Cas13 in human cells,” says Alejandro Méndez-Mancilla, PhD, a postdoctoral scientist in the lab and co-first author of the study.

Last week, a young woman with sickle cell anemia became the first person in the United States to have her cells altered with CRISPR gene editing technology. Here’s what that means for the future treatment of genetic diseases.

The longest-lived leaves in the plant kingdom can be found only in the harsh, hyperarid desert that crosses the boundary between southern Angola and northern Namibia. A desert is not, of course, the most hospitable place for living things to grow, let alone leafy greens, but the Namib Desert — the world’s oldest, with parts receiving less than 2 inches of precipitation a year — is where Welwitschia calls home. Sign up for The Morning newsletter from the New York Times In Afrikaans, the plant is.

“Balancing that, I clearly state that my goal is not longevity, not even modest longevity. It’s just reversal of diseases of aging, which really is classic medicine. Q: Which takes me to the next question: do we even know how to aim at life extension? I don’t think we do. I think if we get serious aging reversal, it’s something that we can continue to improve on, just like we improved on transportation from the first wheel to rocket ships,” I’ll be honest, I disagree as we have some improvement in humans indicated from TRIM and TAME and plasma filtering. Church’s work is very important though.

Professor of Genetics at Harvard Medical School and one of the most prominent geroscientists, George Church works on gene therapies that can potentially reverse age-related diseases. We had the opportunity to interview this prolific researcher and entrepreneur, who is involved in dozens of startups on topics ranging from the current state of gene therapy to his recent attempt to auction off his genome, one of the first sequenced human genomes in the world, as an NFT.

What have been the successes and the failures of gene therapy in recent years? What do you expect to happen in the next few years?

Continue reading “George Church on Gene Therapies and Longevity” »

“Our study raises the possibility of using therapeutic drugs, gene editing, or other strategies to make epigenetic modifications that tap into the latent regenerative capacity of inner ear cells as a way to restore hearing,” said Segil. “Similar epigenetic modifications may also prove useful in other non-regenerating tissues, such as the retina, kidney, lung, and heart.”

Scientists from the USC Stem Cell laboratory of Neil Segil have identified a natural barrier to the regeneration of the inner ear’s sensory cells, which are lost in hearing and balance disorders. Overcoming this barrier may be a first step in returning inner ear cells to a newborn-like state that’s primed for regeneration, as described in a new study published in Developmental Cell.

“Permanent hearing loss affects more than 60 percent of the population that reaches retirement age,” said Segil, who is a Professor in the Department of Stem Cell Biology and Regenerative Medicine, and the USC Tina and Rick Caruso Department of Otolaryngology – Head and Neck Surgery. “Our study suggests new gene engineering approaches that could be used to channel some of the same regenerative capability present in embryonic inner ear cells.”

Continue reading “Stem Cell Scientists Explore the Latent Regenerative Potential of the Inner Ear” »

Disrupting a gene responsible for pigments allowed experts in Kobe, Japan to create albino opossum offspring.

This study builds on an earlier paper by the Rothstein lab that looked at the most common genetic cause of ALS, a mutation in the C9orf72 gene (also referred to as the “C9 mutation”). There, they showed that the C9 mutation produced defects in a structure called the nuclear pore that is responsible for moving proteins and other molecules in and out of the nucleus of cells.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal degenerative disease affecting the nerve cells in the brain and spinal cord responsible for controlling voluntary muscle movement. “Sporadic” or non-inherited ALS, accounts for roughly 90% percent of cases, and 10% of cases are due to known genetic mutations. By studying lab-grown neurons derived from skin or blood cells from 10 normal controls, eight with an ALS causing mutation, and 17 with non-inherited ALS, researchers have found a possible starting point for the dysfunction that causes the disease. The study, which was published in Science Translational Medicine, was funded in part by the National Institute for Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

Using a library of ALS patient-derived cells, the research team led by Jeffrey Rothstein, M.D., Ph.D., at Johns Hopkins University School of Medicine, Baltimore, developed induced pluripotent stem cell (iPSC)-derived neurons from the patients’ cultured cells to discover a common defect regardless of whether the cell came from persons with inherited or non-inherited ALS. They report that in ALS nerve cells, there is an accumulation of a protein called CHMP7 in the nucleus of cultured nerve cells as well as in ALS samples from the brain region that controls movement. Treatments that decrease the amount of CHMP7 in the cultured cells prevented a series of abnormalities that are characteristic of ALS.

Continue reading “Researchers identify a cellular defect common to familial and sporadic forms of ALS” »

Despite years of efforts, malaria remains a major health problem. The mosquito-borne parasitic disease sickens more than 200 million people every year and kills more than 400000, many of whom are children.

For the first time, scientists have shown that a new kind of genetic engineering can crash populations of malaria-spreading mosquitoes.

In the landmark study, published Wednesday in the journal Nature Communications, researchers placed the genetically modified mosquitoes in a special laboratory that simulated the conditions in sub-Saharan Africa, where they spread the deadly disease.

Continue reading “How An Altered Strand Of DNA Can Cause Malaria-Spreading Mosquitoes To Self-Destruct” »

A reverse genetics approach determined that seven genes are required together for normal cell division in a genomically minimal cell; these include two known cell division genes, ftsZ and sepF, a hydrolase of unknown substrate, and four genes that encode membrane-associated proteins of unknown function.