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...editor-based clinical trial for SCD in 2022 and Editas Medicine starting a Cas12-based clinical trial for... no longer an accurate descriptor; progress in clinical therapy is more fitting, so it is time to update... approved or have made significant progress in clinical trials.     Figure 1: Types of delivery...some solid tumors are currently in early-phase clinical trials and have shown promising preliminary results...introduction of the cancer-fighting component, CAR. Clinical trials are underway to explore CRISPR’s capacity...for these diseases was sponsored by Vertex Pharmaceuticals and CRISPR Therapeutics. Data shared from these...-Cas construct targeting the diseased allele specifically. Early-stage trials showed a high success rate...

...Institute for Biological Studies) Multiple uses: From multiplexing to multiscaling NIR-shifted spectrum...and iGECI calcium indicator (Shemetov et al., 2021). In addition to FRET, intensiometric calcium indicators...biosensors for multiscale imaging. Nat Commun 7, 12405 (2016). Qian, Y. et al. A genetically encoded near-infrared...Shemetov, A.A. et al. A near-infrared genetically encoded calcium indicator for in vivo imaging. Nat Biotechnol...photoreceptors incorporating biliverdin IXα (BV) autocatalytically. Fortunately for probe developers and users...NIR FPs and biosensors can be imaged at spatial scales from sub-cellular to whole-body in small animals...performance, and applications of near-infrared calcium indicators in this recent review (Shcherbakova ...

...Volume: < 0.05 ml Skill required: advanced Intrathecal Intrathecal (IT) injections are probably the most advanced...location requires a lot of skill and anatomical knowledge. Intrathecal injections are used for a wide array...experiments. Some of these techniques are what we call “beginner”, or injections that are easy to pick ...easier of the two, but it actually requires more technical skill to place the needle in the correct vein ...institutional oversight is required. Restraint: mechanical restraint or anesthesia Location: tail vein or...you might after getting a vaccine. Restraint: mechanical restraint Location: thigh Gauge: 25–27 Volume...xenograft models. Restraint: back scruffing or mechanical restraint Location: back or hind legs Gauge: ...

...per gene approach that has been the historical standard. Specifically, in our recent publications, we used...these “variants of unknown significance” (sometimes called “VUS”) function is unknown. How can we make a decision... if the majority of information on each cancer clinical sequencing report includes rare variants that ...characterization For many years, we’ve hoped that large scale laboratory-based functional experiments that classify...from testing this hypothesis: There was no large scale, broadly available collection of mutant cDNA clones... variants across a large number of genes as systematically as possible. In developing these assays, we...tumorigenesis assays, drug epistasis assays, and morphological profiling can be used as generalizable strategies...

...understanding of complex biological processes. Many tools exist to perturb biological function in a direct...However, recent work has called this prevalent assumption into question. Specifically, CRISPR-generated mutants...limitations of any technique in the context of the biological question. For example, while gene knockouts have...makes traditional knockouts unattractive from a practical perspective. Therefore, techniques that function...Figure 1: Schematic of an RNAi-inducing transgene. Typically, the desired target of RNAi is expressed as inverted...cannot be used to investigate essential genes. Historically, gene silencing methods were thought to be afflicted...genes of interest to trigger RNAi activation. A typical RNAi experiment can be divided into three fundamental...

...their localization and expression. Qiu saw that inhibition of the PV neurons resulted in mechanical allodynia...Glutamate sensing reporters Abhi Aggarwal is a postbaccalaureate research technician in Kaspar Podgorski’s ... post-transfection, excited at 505 nm (right). Scalebar represents 100 µm. Image from Abhi Aggarwal. ...fourth year Ph.D. candidate at the University of California, Irvine where she studies opioid use disorder...will image these neurons using GCaMP7, measuring calcium signaling related fluorescence during morphine ... disorder,” says Hubbard. Figure 3: 20x confocal image of the periaqueductal gray (PAG), with red...Elizabeth Hubbard.   Haoyi Qiu: Pain response in mechanical allodynia Haoyi Qiu is a M.Sc. student at McGill...

...of the FRET pair. Since many biological processes occur within the typical FRET range, FRET efficiency ...nanometers of each other, or measure the tension in the helical structure of spider silk, or the activity of a ...Fluorescence Resonance Energy Transfer. Unlike the typical excitation and emission of an excited fluorophore...donor fluorophore to the acceptor fluorophore. The typical steps in FRET are: 1. Donor fluorophore excitation... between the fluorophores and serves as a small-scale ruler to measure distances that are too miniscule...Experiments using intermolecular FRET probes are typically used for studying protein-protein interactions...with an intermolecular probe is often either impractical (for biomolecules that are not proteins) or would...

...full support of local law enforcement, and, although there was at least one person vocally protesting us...Stephanie Hays, a researcher at the University of California Berkeley. It’s been half a year since the march...Alina Chan is a postdoctoral researcher at Harvard Medical School working on human artificial chromosomes....rains, it was weather befitting of the ominous political climate in which American scientists find themselves...don't line up with the scientific consensus and calling for billions of dollars in cuts to important research...science, I loved the idea and decided to go. At my local March for Science in Albany, NY, many tables were...scientist at the University of Colorado, Anschutz Medical Campus.  He studies viruses including HIV and is...

...the undesirable side products generated during chemical synthesis of these molecules. To make large amounts...will get you started (Obst et al., 2017)! It is specifically curated for protein expression in K. phaffii... on using K. phaffii, then the MoClo YTK Kit specifically designed for S. cerevisiae is at your service...plant-specific parts you‘ll need, including sub-cellular localization signals, plant markers, and reporters (Engler... arena! The Mammalian Toolkit was engineered specifically for the types of expression and integration ... AAV delivery. While Fragmid developers were specifically testing CRISPR tools, it should be easy enough... MK system was used successfully for protein localization and transport studies in HEK cells, recombinant...

...Spatially Confined Persistent Diradical Emitter. Journal of the American Chemical Society, 145(25), 13615–13622... Andrew York, Maria Ingaramo, and their team at Calico Life Sciences recently set out to do just that ... many organisms) are opaque, which makes most biomedical applications of these tools difficult or impossible...some previous attempts at magnetic control of biological systems (Wheeler et al., 2016; Duret et al., ... were very small or were possible only in non-biological conditions. So, they decided to search for a ...removed (Figure 1). At first, Andrew and Maria were skeptical. The team was careful to test the possibility ...record of developing new microscopy tools for biological applications across a wide range of topics. He...

...Foundation, an organization working to advance biological engineering openly so as to benefit all people...with the BioBricks Foundation to distribute the physical DNA samples, for when that's the preferred mode...parts must flow.' People must be able to use genetically encoded functions - the words in our language...operating system for engineering an entire cell. Typically when people use plasmids, they are trying to do...the entirety of a cell. That's a big long-term technical challenge. We have a strategy that organizes how... engineering of the central dogma at the genome scale, it's going to be tricky to tame the rest of a cell...gates collection of parts implements the basic logical functions, which we know and love. Boolean is in...

...the gut side of things, the authors optigenetically and chemically excited a class of enteroendocrine ...behavior, or the animals being monitored were physically hooked up to invasive, cumbersome systems during...and stimulate or manipulate responses through neurological means like electric stimulation, drug administration...and whistles. The fibers are made from a process called thermal drawing, essentially where blocks of polymers... added - the ‘bells and whistles’ – including microscale light emitting diodes, thermal sensors, and microfluidic... previous implementation of optogenetic tools, calcium sensors, and other common neuroscience tools into...programmable microcontroller, NeuroStack coordinates optical stimulation of its associated fibers across multiple...

...higher specificity and reduced technical variability compared to chemical tracers. rAAV2-retro also has...memory, a special type of memory which includes autobiographical events (see Jin & Maren, 2015). Directional...Further, the connections between regions are often reciprocal, forming a neuronal loop which is activated and...pathways in neurons. Anterograde transport is typically used for the trafficking of organelles, such as... with other neuroscience methods such as electrophysiological recordings. The origins of these methods...serotypes, have been found naturally or have been genetically engineered to have differences in their capsid...plasmids at Addgene). The Gradinaru Lab at the California Institute of Technology generated novel AAVs ...

...Miller-Rhodes from the University of Rochester Medical Center.  You’ve probably heard of Forster Resonance...used the method to interrogate the subcellular localization of interactions between basic leucine zipper...it requires can lead to aberrant subcellular localization of the studied PIPs. The straightforward nature...2018), the generation of such resources in less genetically tractable organisms lags behind. BiFC can also...to the N- and C-terminal end of each PIP and empirically test which combination provides the best fluorescent...counterparts using western blotting. The subcellular localization of BiFC constructs should also be compared against...example), as this can also be perturbed by supraphysiological expression levels. BiFC quantification This...

... tools for all-optical electrophysiology A major challenge in the field of all-optical electrophysiology...response to blue light, which will ultimately co-localize the VP64 transactivator with a dCas9 that has ...expression Brilliant technologies adopt basic biological concepts and employ them in creative and innovative...protein multimerization is seen in many important biological contexts, such as the enhancement of transcriptional... of a transcription factor to a promoter and localization of a protein via the presence of multiple copies...system occurs via antibody-peptide labeling; specifically, cognate peptide epitopes fused to the protein...fluorescent and luminescent siganls and a ratio is calculated (the BRET ratio), which allows for compensation...

... patients, specifically children and patients with skin disorders for research and clinical trials, as...system thus provides a practical way to generate transgene-free, virus-free clinical grade hiPSCs from easily...22422317. 6. Diecke, S., et al., Recent technological updates and clinical applications of induced pluripotent...Their work opened up vast possibilities for the clinical and therapeutic applications of iPSCs. The generation...SOX2, KLF4, and C-MYC [1]. For the derivation of clinical grade hiPSCs, reprogramming methods that do not...therapy trials and remains a safety concern in the clinical field [4]. Three major reprogramming methods are... are considered when generating hiPSCs for clinical purposes: mRNA transfection- this allows transient...

...D) teams at pharma companies carry out preclinical and clinical research to discover and test the best...molecular behaviors of chemicals and proteins to learn how a particular drug or medical device works. This... consulting? Healthcare consultants advise pharmaceutical companies, biotech start-ups, health insurance...efficient ways of delivering healthcare. Clients typically engage consultants as short-term experts to work...different kinds of challenges that consultants get called upon to tackle, depending on the part of the company...acquisitions of or collaborations with other companies. Medical Affairs groups work on building awareness among...among physicians and scientists about clinical research, drugs, the diseases they can treat, and diagnostic...

...next logical step after technical mastery. However, being a great scientist doesn’t automatically translate...transition While a PhD equips you with exceptional technical skills, transitioning into management often means...stepping into unfamiliar territory. Unlike solving technical problems in the lab, management involves a different...time, I discovered that I not only enjoyed the technical aspects of my work but also found fulfilment in...your team's—can lead to frustration. Clinging to technical tasksDelegation can feel unnatural for those accustomed...myself to focus on my core responsibilities, which typically revolved around the broader vision rather than...insights, lessons from their experiences, and practical advice for overcoming challenges. Experimenting...

...revolves around synthetic humans called replicants which are genetically engineered by a powerful corporation...fused a catalytically impaired Cas9 protein to a DNA-editing enzyme to generate the prototypical base editor...STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES. The Journal...Rallapalli, a graduate student at the University of California, San Diego. The revolution in genetic engineering...technology led to the development of many important medical and agricultural products. But it also made SciFi...break at the target genomic location. This is typically followed by non-homologous end-joining that results...sees the USS Enterprise crew fight against a genetically engineered superhuman Khan. The novel, Inferno...

...intramuscular (IM), intrathecal (IT), and intravenous delivery (IV). In mice, IV injections are typically administered...rather than being geographically constrained to the brain. In cases where it’s critical to minimize or eliminate...crossing into the brain. While helpful from a biological standpoint, it makes delivering AAVs to the brain...throughout the organism to target large or diffuse biological structures. Of primary interest here are systemic...peripheral nervous system (PNS). (Capsids, if you recall, are the outer shell of an AAV vector, which determine...Where do they come from? Systemic capsids are typically derived from AAV9, which is one of a handful of...capsid applications. For example, AAV-PHP.eB is typically administered at a total dose between 1 x 1011 ...