Lifeboat Foundation

Engineered vesicular stomatitis virus (VSV) pseudotyping offers an essential method for exploring virus–cell interactions, particularly for viruses that require high biosafety levels. Although this approach has been employed effectively, the current methodologies for virus visualization and labeling can interfere with infectivity and lead to misinterpretation of results. In this study, we introduce an innovative approach combining genetic code expansion (GCE) and click chemistry with pseudotyped VSV to produce highly fluorescent and infectious pseudoviruses (clickVSVs). These clickVSVs enable robust and precise virus–cell interaction studies without compromising the biological function of the viral surface proteins. We evaluated this approach by generating VSVs bearing a unique chemical handle for click labeling and assessing the infectivity in relevant cell lines.

Despite exciting advances in gene editing, the efficient delivery of genetic tools to extrahepatic tissues remains challenging. This holds particularly true for the skin, which poses a highly restrictive delivery barrier. In this study, we ran a head-to-head comparison between Cas9 mRNA or ribonucleoprotein (RNP)-loaded lipid nanoparticles (LNPs) to deliver gene editing tools into epidermal layers of human skin, aiming for in situ gene editing. We observed distinct LNP composition and cell-specific effects such as an extended presence of RNP in slow-cycling epithelial cells for up to 72 h. While obtaining similar gene editing rates using Cas9 RNP and mRNA with MC3-based LNPs (10–16%), mRNA-loaded LNPs proved to be more cytotoxic. Interestingly, ionizable lipids with a p K_a ∼ 7.1 yielded superior gene editing rates (55%–72%) in two-dimensional (2D) epithelial cells while no single guide RNA-dependent off-target effects were detectable. Unexpectedly, these high 2D editing efficacies did not translate to actual skin tissue where overall gene editing rates between 5%–12% were achieved after a single application and irrespective of the LNP composition. Finally, we successfully base-corrected a disease-causing mutation with an efficacy of ∼5% in autosomal recessive congenital ichthyosis patient cells, showcasing the potential of this strategy for the treatment of monogenic skin diseases. Taken together, this study demonstrates the feasibility of an in situ correction of disease-causing mutations in the skin that could provide effective treatment and potentially even a cure for rare, monogenic, and common skin diseases.

Engineers at the University of California San Diego have developed modular nanoparticles that can be easily customized to target different biological entities such as tumors, viruses or toxins. The surface of the nanoparticles is engineered to host any biological molecules of choice, making it possible to tailor the nanoparticles for a wide array of applications, ranging from targeted drug delivery to neutralizing biological agents.

The beauty of this technology lies in its simplicity and efficiency. Instead of crafting entirely new nanoparticles for each specific application, researchers can now employ a modular nanoparticle base and conveniently attach proteins targeting a desired biological entity.

In the past, creating distinct nanoparticles for different biological targets required going through a different synthetic process from start to finish each time. But with this new technique, the same modular nanoparticle base can be easily modified to create a whole set of specialized nanoparticles.

Emmett Short discusses these comments on this episode of Lifespan News.

But first, the mad scientist David Sinclair, this time with Peter Diamandis at Abundance 360, giving more details into human trials for the genetic engineering side of the technology versus the chemical and pill side of the technology. Which would you want more? We’ll also hear David’s thoughts on how AI will affect the advancement of this tech. Spoiler: A lot. I’m going to play the best parts and add my commentary along the way.

The Wistar Institute’s David B. Weiner and collaborators have engineered novel monoclonal antibodies that engage natural killer (NK) cells through a unique surface receptor that activates the immune system to fight against cancer.

In their publication titled, “Siglec-7 glyco-immune binding MAbs or NK cell engager biologics induce potent anti-tumor immunity against ovarian cancers,” published in Science Advances, the team demonstrates the preclinical feasibility of utilizing these new cancer immunotherapeutic approaches against diverse ovarian cancer types, including treatment-resistant and refractory ovarian cancers—alone or in combination with checkpoint inhibitor treatment.

The research started as a collaboration between Wistar’s Drs. Weiner and Mohamed Abdel-Mohsen, who were exploring the development of new glyco-signaling biologic tools that may be important in the fight against cancer.

An FDA advisory panel tended to embrace a new gene therapy treatment from Vertex and CRISPR for sickle cell anemia on Tuesday.

Regenerative medicine and tissue engineering strategies have made remarkable progress in remodeling, replacing, and regenerating damaged cardiovascular tissues. The design of three-dimensional (3D) scaffolds with appropriate biochemical and mechanical characteristics is critical for engineering tissue-engineered replacements. The extracellular matrix (ECM) is a dynamic scaffolding structure characterized by tissue-specific biochemical, biophysical, and mechanical properties that modulates cellular behavior and activates highly regulated signaling pathways. In light of technological advancements, biomaterial-based scaffolds have been developed that better mimic physiological ECM properties, provide signaling cues that modulate cellular behavior, and form functional tissues and organs.

The only cure for painful sickle cell disease today is a bone marrow transplant. But soon there may be a new cure that attacks the disorder at its genetic source.

On Tuesday, advisers to the Food and Drug Administration will review a gene therapy for the inherited blood disorder, which in the U.S. mostly affects Black people. Issues they will consider include whether more research is needed into possible unintended consequences of the treatment.

If approved by the FDA, it would be the first gene therapy on the U.S. market based on CRISPR, the gene editing tool that won its inventors the Nobel Prize in 2020.

A team of researchers has developed a software tool called DANGER (Deleterious and ANticipatable Guides Evaluated by RNA-sequencing) analysis that provides a way for the safer design of genome editing in all organisms with a transcriptome. For about a decade, researchers have used the CRISPR technology for genome editing. However, there are some challenges in the use of CRISPR. The DANGER analysis overcomes these challenges and allows researchers to perform safer on-and off-target assessments without a reference genome. It holds the potential for applications in medicine, agriculture, and biological research.

Their work is published in the journal Bioinformatics Advances on August 23, 2023.

Genome editing, or gene editing, refers to technologies that allow researchers to change the genomic DNA of an organism. With these technologies, researchers can add, remove or alter genetic material in the genome.