Lifeboat Foundation

A team of researchers at Northwestern University has devised a new platform for gene editing that could inform the future application of a near-limitless library of CRISPR-based therapeutics.

Using chemical design and synthesis, the team brought together the Nobel-prize winning technology with therapeutic technology born in their own lab to overcome a critical limitation of CRISPR. Specifically, the groundbreaking work provides a system to deliver the cargo required for generating the gene editing machine known as CRISPR-Cas9. The team developed a way to transform the Cas-9 protein into a spherical nucleic acid (SNA) and load it with critical components as required to access a broad range of tissue and cell types, as well as the intracellular compartments required for gene editing.

Celine halioua drops into a crouch and greets Bocce, a Chihuahua-dachshund mix with soulful brown eyes, like a long-lost friend. “Oh my God, you’re so beautiful!” she chirps. The two have just met in an upstairs room at Muttville Senior Dog Rescue in San Francisco, where light streams in through the open windows and urine occasionally streams onto the floor. About a dozen elderly dogs, none taller than a kneecap, putter around on the gray linoleum or nap on blankets. When Halioua kneels, her dark hair tumbling over her shoulder, Bocce rests his head blissfully in her lap.

A tragedy of human-canine relations is that a 10-year-old dog such as Bocce is old, while a 28-year-old person such as Halioua is in the prime of life. Bocce is one of the lucky ones. Many dogs can only dream of living as long as he likely will, because dog lifespan is inversely correlated with body size. It’s the opposite of the wider pattern in the animal kingdom, where elephants easily outlast mice, which in turn outlive mosquitoes. A Chihuahua can expect roughly 15 years of life; an Irish wolfhound or Great Dane around seven or eight.

Halioua hopes that the startup whose name is emblazoned on her slim black T-shirt— Loyal —can start to fix this bug in humanity’s 14,000-year-plus wolf bioengineering project. The company, which she founded in 2019 and leads as CEO, is developing drugs to delay aging in dogs and extend their healthy lifespan. She has raised around $58 million and has two drugs in development. In a few years, she hopes to have the first commercial drug—for any species—to state on the label that it delays aging or extends lifespan. That alone would be a triumph, but Halioua sees it as a springboard to a still greater feat: creating similar drugs for humans.

https://youtube.com/watch?v=Pr5aRhEIE9A

‎Researchers from the Chinese Communist Party (CCP) claimed in a recently published study to have developed a gene editing method that is supposed to be “more efficient and safer” than the technique used so far.

But there is a lot behind gene editing, so let’s look at what it is all about and its risks and applications.
—————————
#ChinaRevealed #ChinaNews

A study led by researchers from the Institute Cajal of Spanish Research Council (CSIC) in Madrid, Spain in collaboration with the Bioengineering Department of George Mason University in Virginia, U.S. has updated one of the world’s largest databases on neuronal types, Hippocampome.org.

The study, which is published in the journal PLOS Biology, represents the most comprehensive mapping performed to date between neural activity recoded in vivo and identified neuron types. This major breakthrough may enable biologically meaningful computer modeling of the full neuronal circuit of the hippocampus, a region of the brain involved in memory function.

Circuits of the mammalian cerebral cortex are made up of two types of neurons: Excitatory neurons, which release a neurotransmitter called glutamate, and inhibitory neurons, which release GABA (gamma-aminobutanoic acid), the main inhibitor of the central nervous system. “A balanced dialogue between the ‘excitatory’ and ‘inhibitory’ activities is critical for brain function. Identifying the contribution from the several types of excitatory and inhibitory cells is essential to better understand brain operation,” explains Liset Menendez de la Prida, the Director of the Laboratorio de Circuitos Neuronales at the Institute Cajal who leads the study at the CSIC.

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists working on CRISPR/Cas9-mediated gene editing technology have developed a method to increase efficiency of editing while minimizing DNA deletion sizes, a key step toward developing gene editing therapies to treat genetic diseases.

CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used like a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. By modifying gene function, scientists hope to treat genetic diseases by halting a diseased cell’s ability to continue replicating the defective DNA. CRISPR/Cas9 is the most versatile genetic manipulation available and has a wide range of potential applications. While CRISPR/Cas9 mainly generates short insertions or deletions at the target site, it may also make large DNA deletions around the specific target site. These large deletions cause safety concerns and may decrease functional editing efficiency.

The WFIRM team is looking for ways to reduce the chances of this happening. The research described in their recent paper, published recently in Nucleic Acids Research, sought to address the generation of unpredictable on-target long DNA deletions and find a way to guard against them, said lead author Baisong Lu, Ph.D., of WFIRM.

Water Droplets Hold the Secret Ingredient for Building Life. Chemists uncover key to early Earth chemistry, which could unlock paths to speed up chemical synthesis for…

A team of researchers at Northwestern University has devised a new platform for gene editing that could inform the future application of a near-limitless library of CRISPR-based therapeutics.

Using chemical design and synthesis, the team brought together the Nobel-prize winning technology with therapeutic technology born in their own lab to overcome a critical limitation of CRISPR. Specifically, the groundbreaking work provides a system to deliver the cargo required for generating the gene editing machine known as CRISPR-Cas9. The team developed a way to transform the Cas-9 protein into a spherical nucleic acid (SNA) and load it with critical components as required to access a broad range of tissue and cell types, as well as the intracellular compartments required for gene editing.

The research, published today in a paper titled, “CRISPR Spherical Nucleic Acids,” in the publication Journal of the American Chemical Society, and shows how CRISPR SNAs can be delivered across the cell membrane and into the nucleus while also retaining bioactivity and gene editing capabilities.

This video is the 1st of a series of “What is Aging” webinars that aims to unravel what aging is, how we age, why we age, and how to reverse it.

We welcome Jason C. Mercurio, MFE, Dr. Jose Cordeiro, and Dr. Ian Hale to discuss the topic.

Continue reading “Aging is a complex, multidimensional, non-linear and widely misunderstood reversible process” »

Accurate detection and manipulation of endogenous proteins is essential to understand cell biological processes, which motivated laboratories across cell biology to develop highly efficient CRISPR genome editing methods for endogenous epitope tagging (Auer et al., 2014; Nakade et al., 2014; Lackner et al., 2015; Schmid-Burgk et al., 2016; Suzuki et al., 2016; Nishiyama et al., 2017; Artegiani et al., 2020; Danner et al., 2021). Multiplex editing using NHEJ-based CRISPR/Cas9 methods remains limited because of the high degree of cross talk that occurs between two knock-in loci (Gao et al., 2019; Willems et al., 2020). In the current study we present CAKE, a mechanism to diminish cross talk between NHEJ-based CRISPR/Cas9 knock-ins using sequential activation of gRNA expression. We demonstrate that this mechanism strongly reduces cross talk between knock-in loci, and results in dual knock-ins for a wide variety of genes. Finally, we showed that CAKE can be directly applied to reveal new biological insights. CAKE allowed us to perform two-color super-resolution microscopy and acute manipulation of the dynamics of endogenous proteins in neurons, together revealing new insights in the nanoscale organization of synaptic proteins.

The CAKE mechanism presented here creates a mosaic of Cre_ON and Cre_OFF knock-ins, and the number of double knock-in cells depends on the efficacy of each knock-in vector. Therefore, to obtain a high number of double knock-in cells, the efficacy of both the Cre_ON and Cre_OFF knock-in vector must be optimized. We identified three parameters that regulate the efficacy for single and double knock-ins in neurons. First, the efficacy of gRNAs varies widely, and even gRNAs that target sequences a few base pairs apart in the same locus can have dramatically different knock-in rates (Willems et al., 2020; Danner et al., 2021; Fang et al., 2021; Zhong et al., 2021). Thus, the efficacy of each individual gRNA must be optimized to increase the chance of successful multiplex labeling in neurons. gRNA performance is dependent on many factors, including the rate of DNA cleavage and repair (Rose et al., 2017; Liu et al., 2020; Park et al.