Lifeboat Foundation

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.

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.

Bioengineered bacteria sneak past solid tumor defenses to guide CAR T cells’ attacks.

For the first time in the company’s 40-year history, Liebherr have converted one of their R 9,400 excavators from a conventional diesel to an electric powertrain.

The re-powered mining machine was commissioned at Fortescue’s Christmas Creek mine site in Western Australia – but what’s more significant is that the conversion was done during the standard service life of the machine.

“The modular design of Liebherr equipment makes it possible to repower existing diesel excavators to new zero emission configurations, such as electric powertrains,” explains Oliver Weiss, Executive Vice President of R&D, Engineering, and Manufacturing for Liebherr Mining. “This means that the diesel equipment customers buy today is also future-proofed for many years to come. The fact that we can ease the transition from traditional to decarbonized mining fleets for our customers is one of the key strategies of the Liebherr Zero Emission Mining Program.”

Treating complex diseases such as skin cancer often requires simultaneous administration of multiple anticancer drugs. The delivery of such life-saving therapeutic drugs has evolved with the rise of nanotechnology-based drug carriers. Nanoplatforms offer numerous advantages, including increased bioavailability, lowered dosages, and improved biodistribution.

Now a team of researchers, led by Professor Myoung-Hwan Park from Sahmyook University in South Korea, has developed a light-responsive nanofiber-based novel drug delivery system (DDS) targeting skin cancer. The DDS was studied in a detailed manner, beginning with its synthesis and characterization to its biocompatibility, drug release profile, and efficacy against skin cancer. These research findings are published in the Journal of Drug Delivery Science and Technology.

Explaining the motivation behind the present research, Dr. Park states, “Conventional drugs can be efficiently delivered in a controlled manner through nano-engineered platforms, and such an approach increases the overall effectiveness of the treatment. This approach improves outcomes in cancer drug therapy by ensuring precise delivery at optimal dosages.”

Tissue engineering, which involves the use of grafts or scaffolds to aid cell regeneration, is emerging as a key medical practice for treating volumetric muscle loss (VML), a condition where a significant amount of muscle tissue is lost beyond the body’s natural regenerative capacity. To improve surgical outcomes, traditional muscle grafts are giving way to artificial scaffold materials, with MXene nanoparticles (NPs) standing out as a promising option.

MXene NPs are 2D materials primarily composed of transition-metal carbides and nitride. They are highly electrically conductive, can accommodate a wide range of functional groups, and have stacked structures that promote cell interactions and muscle growth. While there have been practical demonstrations in the laboratory showcasing their ability to promote the reconstruction of skeletal muscles, the specific mechanism by which they do so remains unclear.

To address this gap, Associate Professor Yun Hak Kim from the Department of Anatomy and Department of Biomedical Informatics, alongside Professors Suck Won Hong, and Dong-Wook Han from the Department of Cogno-Mechatronics Engineering at Pusan National University developed nanofibrous matrices containing MXene NPs as scaffolds. They used DNA sequencing to reveal the genes and biological pathways activated by MXene NPs to aid in muscle regeneration.

Advanced Science is a high-impact, interdisciplinary science journal covering materials science, physics, chemistry, medical and life sciences, and engineering.

Jeff Desjardins, Editor-in-Chief of Visual Capitalist, joins OPTO Sessions to discuss the profound and far-reaching potential of CRISPR and gene editing technology, which he believes could impact fields as diverse as oncology, agriculture and materials science.

On 8 December, the US Food and Drug Administration (FDA) approved two cell-based gene therapies for the treatment of sickle cell disease. The decision marked a watershed moment in the history of healthcare, being the first time that gene therapies have won FDA approval.

One of the treatments, Casgevy, is the result of a collaboration between CRISPR Therapeutics [CRSP] and Vertex Pharmaceuticals [VRTX]. The other, Lyfgenia, was developed by bluebird bio [BLUE].

Anthrobots: These remarkable spheroid-shaped multicellular biological robots, or biobots, are not the products of advanced robotics laboratories but are instead born from the inherent potential of adult human somatic progenitor seed cells.

Advanced Science is a high-impact, interdisciplinary science journal covering materials science, physics, chemistry, medical and life sciences, and engineering.