Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: bioengineering – Page 51

Engineered Immune Cell Improves Treatment of Ovarian Cancer

Cancer is a malignant disease referring to the uncontrollable proliferation of mutated cells. Millions of individuals are affected by cancer each year in the United States alone. Unfortunately, treatment is limited due to the heterogeneity of the disease and different components, which drive the disease to progress. The proliferation of cells can occur anywhere in the body including different organs such as breast, lung, pancreas, and head and neck. Cancer can also affect the reproductive tract in both men and women including the testes and ovaries, respectively. Particularly, ovarian cancer is linked with breast cancer and can result in infertility due to late detection. Due to limited therapeutic efficacy in ovarian cancer, more research is necessary for a meaningful solution. Different groups are working to more effectively target ovarian cancer through different biologic approaches.

Dr. David B. Weiner and his team from the Wistar Institute recently published an article in Science Advances demonstrating enhanced immunotherapeutic effects in ovarian cancer patients. Immunotherapy refers to a form of cancer therapy that directs the immune system to attack the tumor. In many immunotherapies, immune cells, such as T cells, are activated to kill tumors. This is a unique approach to target cancer compared to chemotherapy or radiation, which tries to directly kill tumor cells and elicit an immune response. Immunotherapy allows the immune system to recognize the tumor and react through the body’s immune system. One prominent immune cell includes natural killer (NK) cells which responsible for initial lying or killing of foreign particles. Novel work has tried to engineer NK cells to target tumors by recognizing unique receptors on its surface.

Weiner’s team and collaborator, Mohamed Abdel-Mohsen, have engineered monoclonal antibodies to engage NK cells to lyse cancer. Interestingly, the team demonstrated this immunotherapeutic regimen optimized preclinical output in mice when combined with checkpoint inhibitors, another type of immunotherapy. The group engineered antibodies to target a glyco-immune marker on most NK cells referred to as Sialic acid-binding immunoglobulin-type lectin (Siglec-7). The novel combination strategy targets NK cells through Siglec-7 and T cells to optimize immune response against tumor cells. The monoclonal antibody (mAb) targeting Siglec-7 allows NK cells to become activated and kill ovarian cancer cells without killing non-cancer cells, which improve specificity and reduce toxicity for patients. Consequently, this antibody resulted in generating a new class of NK cell engagers (NKCE).

DNA repair discovery might improve biotechnology: Research

Washington [US], March 5 (ANI): A team of researchers from Michigan State University’s College of Veterinary Medicine made a discovery that may have significance for therapeutic gene editing strategies, cancer diagnostics and therapies and other advancements in biotechnology. Kathy Meek, a professor in the College of Veterinary Medicine, and collaborators at Cambridge University and the National Institutes of Health have uncovered a previously unknown aspect of how DNA double-stranded breaks are repaired.

A large protein kinase called DNA-PK starts the DNA repair process; in their new report, two distinct DNA-PK protein complexes are characterized, each of which has a specific role in DNA repair that cannot be assumed by the other.

“It still gives me chills,” says Meek. “I don’t think anyone would have predicted this.”

Re-Engineered Pseudoviruses for Precise and Robust 3D Mapping of Viral Infection

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.

Lipid Nanoparticle-Mediated Hit-and-Run Approaches Yield Efficient and Safe In Situ Gene Editing in Human Skin

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 Ka ∼ 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.

‘Plug and play’ nanoparticles could make it easier to tackle various biological targets

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 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.

At Abundance 360, David Sinclair made quite a number of encouraging comments about the future of aging research, including methods of resetting epigenetics to a youthful state

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.

New NK cell engaging immunotherapy approaches to target and potentially treat recalcitrant ovarian cancer

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 ,” 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.

Extracellular Matrix-Based Biomaterials for Cardiovascular Tissue Engineering

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.

A new cure for sickle cell disease may be coming. FDA advisers will review it next week

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.