Logan Lawrence’s Post

Interesting reading on #secretomic and #transcriptomic analysis that gives us another point of view when designing #celltherapy, defining #biomarker or new #targetedtherapies.

SEC-seq: technique developed by Dino Di Carlo and colleagues to link protein secretion to gene expression at single cell level via use of nanovials.

I think it is important to remember that it is still early days for single cell profiling. I was reviewing comment from AGBT - Advances in Genome Biology and Technology in 2017 and it struck me that there was a quote from Michael Talkowski about the future of single cell having the promise of revealing new insights and becoming mainstream. It has really only been a few years of single cell technologies being mainstream and we are just now seeing new technologies like Deepcell emerging in this space. The next 3 to 5 years should be exciting for both #singlecellanalysis and #spatialbiology

This is a new way to work with single cells - alternative to microfluidics. Fits well with multi-omics approach; useful for cell line development too.

UCLA press release on our SEC-seq technique, which was published today in Nature Nanotechnology. We apply #nanovials, bowl-shaped microscale hydrogel particles, to detect the secretion of growth factor produced by thousands of individual cells and link this information to the gene expression signature of each of those same single cells. Surprisingly, we found that the mRNA level encoding for the growth factor, vascular endothelial growth factor (VEGF), responsible for induction of blood vessel formation and regeneration of tissue, did not correlate with the level of secretion. Instead we found another set of genes highly correlated with secretion that marked a small sub-population of cells with much higher secretion. We coined the term Vascular Regenerative Signal (VRS) to describe this signature. The VRS also contained some surface marker genes. Some of these genes were reflected by higher protein levels of the VRS cells, which we used to sort the VRS sub-population. The population maintained the highly secretory phenotype and surface marker over at least a week of culture - with implications for therapeutic use! These results should inform how we design the next generation of #celltherapies . Instead of just assuming that inserting a gene to drive higher mRNA levels will lead to more secreted proteins, we need to think about the cell as a holistic system that has other checks and controls on what it secretes and when. We believe this #functionfirst discovery approach can improve outcomes with cell therapies, by directly measuring the final cellular functions that drive therapeutic effect and developing a sophisticated understanding of its origins. SEC-seq stands for Secretion-Encoded single-Cell Sequencing. We designed the approach to be easily accessible to researchers and scientists around the world, since it leverages standard equipment like the 10x Genomics Chromium system with BioLegend's oligo-barcoded antibodies. Sorting of cell-loaded nanovials is conducted with a Sony Biotechnology Inc. SH800S sorter. Nanovials are available from Partillion Bioscience. Congratulations to Shreya Udani, Justin Langerman, Kathrin Plath, Joe de Rutte, Doyeon Felis Koo, SEVANA BAGHDASARIAN, Brian Cheng, Simran Kang, Citra Soemardy for the great teamwork to develop the technology and explore new frontier biology of translational importance. Reach out if you want to try SEC-seq - we'd be happy to help! #labonaparticle #nanotechnology #stemcells #celltherapy #cellandgenetherapy #singlecell #singlecellanalysis #cytometry #flowcytometry #biotechnology #secseq https://lnkd.in/g-uf7P5i

CURRENT AVENUES AND FUTURE PROSPECTS OF NANOBIOTECHNOLOGY Nanobiotechnology is an emerging field that is an intersection of Biotechnology and Nanotechnology. This field has and continues to achieve contribution from various scientific disciplines. Fundamentally, Nanobiotechnology focuses on the manipulation of materials at the nanosize level and successive combination with biomolecules. Nanostructured materials are now being used in various products, pharmaceuticals, cosmetics and industries. The potential of Nanobiotechnology to deal at the nanomolecular level has fostered the development of devices and products with high sensitivity and specificity thus improving performance of various processes, products and devices. Interestingly, nanomaterials function as more than mere tiny versions of the macromaterial. Nanomaterials possess physical and chemical properties different from those of the large-scale material. Their size is sufficiently small to the effect that quantum mechanics dictates some of their properties. Nanobiotechnology currently does and continues to find diverse application. Owing to the fact that nanomaterials are of the same scale as biological molecules, nanomaterials present their possibility of intervention in biological systems. Notably, this includes Medical Nanobiotechnology which permits diagnosis of diseases at an early stage and more cheaply. Additionally, there is hope for individuals having genetic disorders in that through medical nanobiotechnology, gene therapy is possible. Genetic disorders can be prevented or treated by correcting defective genes causative of genetic disorders by delivery of repaired genes or the replacement of defective ones. Through Nanobiotechnology, therapeutic efficacy and safety of drugs can be improved by controlling drug delivery to ensure accuracy of rate and target. This would incredibly reduce cases of medical toxicity and side effects. Notably, Nanobiotechnology presents great potential in effective cancer therapy. Nanoscale systems are also instrumental in the delivery of incompatible drugs. At a quantum level, the reaction of entities (electrons, atoms, molecules) is in response to the information provided to them in their environment. This principle finds expression on nanobiotechnological tissue engineering which aims to restore the normal function of organs and tissues previously diseased or injured. In harmony with the aforementioned principle, cells respond to nano information presented to them in their microenvironment ultimately achieving the goal of tissue regeneration (engineering). This overcomes limitations related to the use of allografts and xenografts. In the food sector, Nanobiotechnology is instrumental in pathogen detection. Nanobiotechnology provides an accurate nanodetection of food pathogens. This fields continues to evolve and present more scientific potential presently and in years to come. #Nanobiotechnology #nanotechnology #nanomedicine

Hello, Dear Connections, As someone interested in the biomedical engineering field, I am excited to share some advancements in nanotechnology that are transforming drug delivery systems. The convergence of nanotechnology and medicine is opening up new frontiers for more effective, targeted, and personalized treatments. Here’s how: 🔬 Precision Targeting Nanotechnology enables the development of drug delivery systems that can precisely target diseased cells, minimizing the impact on healthy tissues. This precision reduces side effects and increases the efficacy of treatments, particularly in cancer therapy. Nanoparticles can be engineered to recognize and bind to specific cell receptors, ensuring that the medication reaches its intended destination. 💡 Enhanced Drug Solubility and Bioavailability Many drugs suffer from poor solubility and bioavailability, limiting their effectiveness. Nanotechnology can enhance the solubility of drugs, allowing for better absorption and improved therapeutic outcomes. Nanocarriers, such as liposomes and polymeric nanoparticles, help in delivering hydrophobic drugs in a more soluble form. ⏳ Controlled and Sustained Release Nanotechnology allows for the design of drug delivery systems that provide controlled and sustained release of medication. This means that drugs can be released at a consistent rate over a prolonged period, reducing the need for frequent dosing and improving patient compliance. The controlled release also ensures a steady therapeutic effect, enhancing the overall treatment process. 🌐 Crossing Biological Barriers One of the significant challenges in drug delivery is crossing biological barriers, such as the blood-brain barrier. Nanoparticles have shown promise in overcoming these barriers, enabling the delivery of drugs to previously inaccessible areas of the body. This advancement opens up new possibilities for treating neurological disorders and brain cancers. 🔍 Future Prospects The future of nanotechnology in drug delivery is incredibly promising. Research is ongoing to develop smart nanoparticles that can respond to environmental stimuli, such as pH or temperature changes, for on-demand drug release. Additionally, integrating nanotechnology with other cutting-edge fields like gene therapy and immunotherapy holds the potential for creating highly personalized treatment regimens. Thank you for reading, and let’s keep pushing the boundaries of biomedical engineering! #BiomedicalEngineering #Nanotechnology #DrugDelivery #HealthcareInnovation #TargetedTherapy #ControlledRelease #FutureOfMedicine

Central dogma needs a recheck In an interesting article in Nature Nanotechnology, researchers at UCLA have raised questions regarding the accepted principle in biology, i.e., DNA encodes RNA and RNA translates to proteins. By extension, more RNA would lead us to believe more protein. Not so. In the study the authors found that the gene expression correlated only weakly with the actual secretion of the growth factor (VEGF-A). This was achieved using a new technique based on nanovials, which are microscopic bowl-shaped hydrogel containers, each of which captures a single cell and its secretions. While activation of the genetic instructions for VEGF-A displayed little correlation with release of the protein, the researchers identified a cluster of 153 genes with strong links to VEGF-A secretion. Many of them are known for their function in blood vessel development and wound healing; for others, their function is currently unknown. One of the top matches encodes a cell-surface protein, IL13RA2, whose purpose is poorly understood. Its exterior location made it simpler for the scientists to use it as a marker and separate those cells from the others. Cells with IL13RA2 showed 30% more VEGF-A secretion than cells that lacked the marker. The results could help make the manufacturing of antibody-based treatments more efficient and define new cellular treatments that would be more effective. The new sequencing technique developed is dubbed SEC-seq, and stands for secretion-encoded single-cell sequencing. https://lnkd.in/dsp5UTyb https://lnkd.in/dThyUWGZ #nanomaterials #vegf #centraldogma #nanovials #emergingtechnologies #nanotechnology

Development of micro-robots that can deliver medication to metastatic tumors Developed by engineers at the Engineers Without Border University of California San Diego, green algae cells are utilised to provide a transportation medium for microrobots, that move through the tissue in the lungs, in order to deliver cancer-fighting medication directly to cancerous tumours. The findings have been published in a paper by Science Advances. The development, has been the production of a collaboration between the labs of Joe Wang and Liangfang Zhang, both professors in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the UC San Diego Jacobs School of Engineering, which has seen the use of both biology and nanotechnology. In order to create the microrobots, the developers chemically attached nanoparticles, that were filled with the drug payload, to the surface of the green algae cells. The algae then disperse within the space of the lung tissue, allowing the nanoparticles to deliver their payload to the tumours. The nanoparticles themselves are made of biodegradable polymer spheres. These are then loaded with the required chemo drug, and coating with red blood cell membranes to prevent an immunological response from the patients immune system. In a statement, Zhengxing Li, PhD student and study co-first author, said: “This coating makes the nanoparticle look like a red blood cell from the body, so it will not trigger an immune response.” Regarding the study, it involved monitoring the responses of mice which had developed melanoma in the lungs. The microrobots were administered to the lungs via a small tube that was inserted into the windpipe. Treated mice experienced a media survival time of 37 days, in relation to the 27 day benchmark of untreated mice. “The active swimming motion of the microrobots significantly improved distribution of the drug to the deep lung tissue, while prolonging retention time,” said Li. “This enhanced distribution and prolonged retention time allowed us to reduce the required drug dosage, potentially reducing side effects while maintaining high survival efficacy.” The next phase of development will see the administering of the drug medium to larger animals with an eventual goal of human trials. 

Are long-standing genetic principles misleading bioengineers? 🧬 UCLA researchers, led by CNSI member and UCLA Henry Samueli School of Engineering and Applied Science professor Dino Di Carlo, have challenged the traditional ‘central dogma’ of biology. In a groundbreaking discovery, Di Carlo and his team have found that the cell-surface protein IL13RA2 plays a pivotal role in boosting VEGF-A growth factor secretion—which drastically reshapes our understanding of cellular behavior. Initially published in Nature Nanotechnology, it not only streamlines antibody-based treatment manufacturing but also holds promise for targeted cellular therapies in conditions like #heartattacks. This study utilized "nanovials"—a technology developed by Di Carlo and available commercially from Magnify Incubator company Partillion Bioscience. Learn more in the link below: https://lnkd.in/g4twmfZ2