Lifeboat Foundation

Acute myeloid leukemia (AML) is a rare and aggressive hematologic malignancy. AML progresses rapidly and is indicated by an excess of immature white blood cells. It is caused by high mutational burden over the span of a person’s life. One signature mutated gene includes the tumor suppressor gene TP53. Normally, TP53 helps make protein to stop oncogenesis or the formation of tumors. However, mutated TP53 loses that function and commonly results in AML. Unfortunately, those that have a TP53 mutation have an extremely aggressive tumor that is resistant to conventional chemotherapy drugs and results in poor prognosis. Other standard treatments include stem-cells transplants, and sometimes targeted drugs such as intracellular pathway inhibitors. Although many treatments are routine and help the patient reduce symptoms, there is no cure. Extensive research is currently being done by researchers and physicians to identify new approaches for AML treatment.

One novel therapy used in other hematologic malignancies includes chimeric antigen receptor (CAR)-T cell therapy. This therapy takes immune T cells (responsible for lysing or kill infections) from the patient or a donor and engineers them to target the tumor. Normally, these T cells would not recognize tumor growth, therefore, the engineered CAR-T cells are programmed to elicit an immune response and recognize surface markers on the tumor to lyse it. This therapy has been successful in other leukemias such as B-cell acute leukemia, and researchers are working to overcome treatment resistant AML using the same approach.

A recent article in EMBO Molecular Medicine, by Drs. Markus Manz, Stephen Boettcher and others, demonstrate that TP53-mutated AML is resistant to CAR-T cell therapy as a single agent, but can be overcome through combination therapy. Manz and Boettcher are principal investigators from the University of Zurich and the Department of Medical Oncology and Hematology at the University Hospital Zurich (USZ) and focus on mechanisms surrounding hematological diseases. The Zurich team first reported why TP53-mutated AML is resistant to CAR-T cell therapy. Using various models, it was noted that the engineered T cells quickly become ‘exhausted’ or inactive due to overstimulation or surrounding stimuli. The team further studied the underlying mechanism in this disease by concluding that TP53-deficient cells caused resistance through several metabolic pathways. Moreover, these pathways including the mevalonate and Wnt pathways were identified to improve therapeutic efficacy.

Researchers at Rutgers and Emory University are gaining insights into how schizophrenia develops by studying the strongest-known genetic risk factor.

When a small portion of chromosome 3 is missing—known as 3q29 deletion syndrome—it increases the risk for schizophrenia by about 40-fold.

Researchers have now analyzed overlapping patterns of altered gene activity in two models of 3q29 deletion syndrome, including mice where the deletion has been engineered in using CRIPSR, and human brain organoids, or three-dimensional tissue cultures used to study disease. These two systems both exhibit impaired mitochondrial function. This dysfunction can cause energy shortfalls in the brain and result in psychiatric symptoms and disorders.

In a recent study published in Nature Communications, researchers developed a modular synthetic biology toolkit for Aspergillus oryzae, an edible fungus used in fermented foods, protein production, and meat alternatives.

Study: Edible mycelium bioengineered for enhanced nutritional value and sensory appeal using a modular synthetic biology toolkit. Image Credit: Rattiya Thongdumhyu/Shutterstock.com.

The advent of CRISPR gene editing, along with nanopore genome sequencing and single-cell RNA sequencing, has allowed the study of host-microbe interactions with newfound accuracy and power. The studies taking advantage of these tools have provided insights with never-before seen precision and, excitingly, have revealed surprising findings on principles of host-microbe interactions. This special issue reviews and interprets host immunological and developmental interactions with the resident microbiome. The articles reflect on evolutionary principles guiding how hosts interact with their commensal microbiota and offer new techniques and directions for research that we hope will advance the field in the years to come.

This issue is available to buy in print. Visit our information for readers page for purchasing options.

New research presented early ahead of this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024, Barcelona, 27–30 April) from a team of researchers in the Netherlands shows how the latest CRISPR-Cas gene editing technology can be used to eliminate all traces of the HIV virus from infected cells in the laboratory, raising hopes of a cure.

Exploring the cutting edge of genetic engineering, the development of programmable recombinases and zinc finger domains is ushering in a new era of precision in DNA manipulation. These advances enable precise genomic alterations, from single nucleotide changes to the insertion of large DNA segments, potentially transforming the landscape of therapeutic gene editing and opening new possibilities in personalised medicine.

UCLA bioengineers create thin, flexible neck device translating larynx muscle movements into audible speech.

Scientists have categorized different types of CRISPR systems into two classes based on how their Cas nucleases function. In class 1 (types I, III, and IV), different Cas proteins form a complex machinery to identify and cut foreign DNA; in class 2 CRISPR systems (types II, V, and VI), a single Cas protein effector recognizes and cleaves DNA.⁹

After characterizing CRISPR’s role as a defense mechanism in bacteria, researchers soon realized that they could harness this system for gene manipulation in any cell. All they needed to do was design a CRISPR gRNA sequence that bound to a specific DNA sequence and triggered the Cas nuclease, which would then cut precisely at that location. With CRISPR, researchers routinely knock out gene function by cutting out a DNA fragment, or they insert a desired genetic sequence into the genome by providing a reference DNA template along with the CRISPR components. While editing eukaryotic cells has been the focus for tackling diseases, many researchers now use CRISPR to edit bacterial communities.

“It’s almost like back to the beginning or back to the origins. There’s some irony in bringing CRISPR back to where it came from,” said Rodolphe Barrangou, a functional genomics researcher at North Carolina State University, who helped characterize the immune function of CRISPR and has been working with it for more than 20 years.

Nanomedicine to Cure All!

Aortic aneurysms are bulges in the aorta, the largest blood vessel that carries oxygen-rich blood from the heart to the rest of the body. Smoking, high blood pressure, diabetes, or injury can all increase the risk of aneurysms, which tend to occur more often in Caucasian male smokers over the age of 65.

“The soft tissues that make up blood vessels act essentially like rubber bands, and it’s the elastic fibers within these tissues that allow them to stretch and snap back,” says Professor Anand Ramamurthi, chair of the Department of Bioengineering in Lehigh University’s P.C. Rossin College of Engineering and Applied Science. “These fibers are produced primarily before and just after birth. After that, they don’t regenerate or undergo natural repair after injury. So when they become injured or diseased, the tissue weakens and causes an aneurysm, which can grow over time. After about seven to 10 years, it typically reaches the rupture stage.”

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