Lifeboat Foundation

Scientists from the German Cancer Research Center (DKFZ) and Heidelberg University have investigated in mice how spreading tumor cells behave at the site of metastasis. Some tumor cells immediately start to form metastases. Others leave the blood vessel and may then enter a long period of dormancy. What determines which path the cancer cells take is their epigenetic status. This was also confirmed in experiments with human tumor cells. The results of the study could pave the way for novel diagnostic and therapeutic applications.

The work appears in Nature Cancer.

What makes cancer so dangerous? Cancer cells that leave the primary tumor to reach distant sites of the body where they may grow into daughter tumors, called metastases. While most primary tumors can be effectively treated, metastases are the real danger. Oncologists estimate that more than 90% of all cancer deaths in solid tumors are due to metastases.

A gene editing tool using a system known as CRISPR-Cas9 has recently been approved by the U.S. Food and Drug Administration (FDA) for sickle cell disease. The drug is known as Casgevy and the media has hailed this treatment as a ‘cure’ for sickle cell anemia patients. While it is still unclear if the drug completely cures these patients, clinical trials show exciting efficacy.

Sickle cell disease is a genetic blood disorder affecting thousands of US citizens. Many of these patients are African American and Hispanic. In sickle cell disease, hemoglobin, a protein in red blood cells that helps carry oxygen throughout the body, is mutated. As a result, blood cells change shape in the form of a sickle, giving the disease its name. Unfortunately, the mutated cells cause disruption of blood flow and prevent other blood cells from delivering oxygen to the body. This disease is extremely rare and can lower the quality of life in patients. Previously, there were limited treatments options including transfusions and medications for pain management. However, Casgevy provides a new option to help treat the patient and relieve pain for over a year after a single treatment.

One-time treatment using Casgevy improved life quality for sickle cell patients. A single-arm trial was conducted at multiple health centers in adults and adolescents. These patients were screened for two vaso-occlusive crises (VOCs) which are described as severely painful events due to a lack of oxygen delivery from sickle cell blood cells blocking blood flow. The primary measure of success in the trial was the number of VOCs after treatment. In total, 44 patients received Casgevy and 33 were able to follow up and be evaluated. Of the 33 patients that made it through the trial, 29 of them did not experience any VOCs for 12 months. This is a 93.5% success rate based on the number of patients that were analyzed. All 44 patients were able to successfully undergo treatment without any graft rejection. In addition, researchers concluded that this treatment was not only effective, but safe with few side effects.

Some human neurons take years to reach maturity; an epigenetic ‘brake’ could be responsible.

Epigenomic analyses suggest promising new approaches for monitoring and treating cancer. What are the analyses uncovering, and how close are they to improving patient outcomes?

Using CRISPR, an immune system bacteria use to protect themselves from viruses, scientists have harnessed the power to edit genetic information within cells. In fact, the first CRISPR-based therapeutic was recently approved by the FDA to treat sickle cell disease in December 2023. That therapy is based on a highly studied system known as the CRISPR-Cas9 genetic scissor.

However, a newer and unique platform with the potential to make large-sized DNA removals, called Type I CRISPR or CRISPR-Cas3, waits in the wings for potential therapeutic use.

A new study from Yan Zhang, Ph.D., Assistant Professor in the Department of Biological Chemistry at the University of Michigan Medical School, and her collaborators at Cornell University develops off-switches useful for improving the safety of the Type I-C/Cas3 gene editor. The study, “Exploiting Activation and Inactivation Mechanisms in Type I-C CRISPR-Cas3 for 3 Genome Editing Applications,” is published in the journal Molecular Cell.

Join us on Patreon! https://www.patreon.com/MichaelLustgartenPhDDiscount Links: Epigenetic, Telomere Testing: https://trudiagnostic.com/?irclickid=U-s3Ii2r7x…

A genetic marker linked to premature aging was reversed in children with obesity during a six-month diet and exercise program, according to a recent study led by the Stanford School of Medicine.

Children’s telomeres—protective molecular “caps” on the chromosomes—were longer during the weight management program, then were shorter again in the year after the program ended, the study found. The research was published last month in Pediatric Obesity.

Like the solid segment at the end of a shoelace, telomeres protect the ends of chromosomes from fraying. In all people, telomeres gradually shorten with aging. Various conditions, including obesity, cause premature shortening of the telomeres.

Gene editing is revolutionizing the understanding of health and disease, providing researchers with vast opportunities to advance the development of novel treatment approaches. Traditionally, researchers used various methods to introduce double strand breaks (DSBs) into the genome, including transactivator-like effectors, meganucleases, and zinc finger nucleases. While useful, these techniques are limited in that they are time and labor intensive, less efficient, and can have unintended effects. In contrast, the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) system (CRISPR/Cas9) is among the most sensitive and efficient methods for creating DNA DSBs, making it the leading gene editing technology.

CRISPR/Cas9 is a naturally occurring immune protective process that bacteria use to destroy foreign genetic material.¹ Researchers repurposed the CRISPR/Cas9 system for genetic engineering applications in mammalian cells, exploiting the molecular processes that introduce DSBs in specific sections of DNA, which are then repaired to turn certain genes on or off, or to correct genomic errors with extraordinary precision.^2,3 This technology’s applications are far reaching, from cell culture and animal models to translational research that focuses on correcting genetic mutations in diseases such as cancer, hemophilia, and sickle cell disease.⁴

Researchers exploit plasmids, the small, closed circular DNA strands native to bacteria, as delivery vehicles in CRISPR/Cas9 gene editing protocols. Plasmids shuttle the CRISPR/Cas9 gene editing components to target cells and can be manipulated to control gene editing activity, including targeting multiple genes at a time. Plasmids can also deliver gene repair instructions and machinery. For example, poly (ADP-ribose) polymerase 1 (PARP1) is an enzyme that drives DNA repair and transcription.⁵ It is a critical aspect of CRISPR/Cas9 gene editing technology in part because it helps repair the DSBs created by the CRISPR/Cas9 system. PARP1 CRISPR plasmids can edit, knockout, or upregulate PARP1 gene expression depending on the specific instructions encoded in the plasmid.

Study co-led by HMS scientist corrects gene mutation involved in inner ear function.