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Category: genetics – Page 227

Modulating pet gut microbiomes for longer, healthier & happier lives — dr. holly ganz, CSO and co-founder, animalbiome.

Dr. Holly Ganz, Ph.D. is Chief Science Officer And Co-Founder of AnimalBiome (https://animalbiome.com/home), a company with a goal of helping cats and dogs lead longer, happier lives by using science to unlock the mysteries of the pet gut microbiome, providing access to genetic data on the health of the gut microbiome, better ways to log health and diet records, and offering remedies to treat chronic digestive disorders.

Dr. Ganz received her PhD from UC Davis Entomology and Evolutionary Ecology, an MS from the Scripps Institution of Oceanography in Marine Biology, UC San Diego and a BS in Biology from George Washington University and has studied the interaction between microbes and their hosts for over 20 years.

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Outbreak and rapid spread of coronavirus disease (COVID-19) caused by coronavirus acute respiratory syndrome (SARS-CoV-2) caused severe acute respiratory syndrome (SARS-CoV-2) that started in Wuhan, and has become a global problem because of the high rate of human-to-human transmission and severe respiratory infections. Because of high prevalence of SARS-CoV-2, which threatens many people worldwide, rapid diagnosis and simple treatment are needed. Genome editing is a nucleic acid-based approach to altering the genome by artificially changes in genetic information and induce irreversible changes in the function of target gene. Clustered, regularly interspaced short palindromic repeats (CRISPR/Cas) could be a practical and straightforward approach to this disease. CRISPR/Cas system contains Cas protein, which is controlled by a small RNA molecule to create a double-stranded DNA gap. Evidence suggested that CRISPR/Cas was also usable for diagnosis and treatment of SARS-CoV-2 infection. In this review study, we discoursed on application of CRISPR technology in detection and treatment of SARS-CoV-2 infection. Another aspect of this study was to introduce potential future problems in use of CRISPR/Cas technology.

Coronavirus disease (COVID-19) was spread in December 2019 and was recognized as a zoonotic disease (Drosten et al., 2017; Andersen et al., 2020). Severe acute respiratory syndrome (SARS) virus was detected in sputum samples in 2003, and advanced stages in fecal samples may have been transmitted to humans by an intermediate host such as bats and civets (Wang and Eaton, 2007; Graham and Baric, 2010). Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can be transmitted from an unknown carrier to a healthy person who could infect many people. SARS-CoV-2 resulted in pneumonia in Wuhan, China, with various symptoms reported. The disease has developed into a pandemic (Wu C. et al., 2020; Wu D. et al., 2020; Guan et al., 2020). Appropriate methods could treat and control the disease. CRISPR/Cas9 was first recognized as a microbial immune system through which these organisms acquire immunity to invading viruses and plasmids (Garneau et al., 2010).

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Heart attacks are the world’s leading cause of death, yet the few treatments available are often expensive and inaccessible. Although that’s been the case for years, the World Health Organization warned back in 2020 heart disease numbers were still on the rise.

Verve Therapeutics says altering human genomes to prevent the buildup of bad cholesterol might be the answer, and is creating what CEO Sekar Kathiresan says may be a permanent solution to heart disease. The company is backed by Google Ventures, according to a report about the breakthrough published Friday in Bloomberg. Verve also counts a Harvard medical professor and an award-winning medical expert among its cofounders.

“We’re on the cusp of potentially transforming that model to a one-and-done treatment,” Kathiresan told the business publication.

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In a study printed in PNAS, researchers have shown that telomerase reverse transcriptase (TERT) can be given to cells in living mice through a viral vector, taking the idea of life-extending gene therapies from science fiction to reality.

Why a cytomegalovirus?

The human cytomegalovirus (CMV) is widely known as an endemic virus that, while usually asymptomatic, is known to cause with harmful effects in babies and older adults. However, some of its properties make this virus suitable for delivering gene therapies. As cytomegaloviruses can carry large genetic payloads and don’t overwrite the DNA of their host cells [1], replacing the genes of these viruses with beneficial DNA may be safer than approaches with more potential off-target effects; development in this area is ongoing, and a phase 1 human clinical trial has already been conducted [2].

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According to a new concept by LMU chemists led by Thomas Carell, it was a novel molecular species composed out of RNA and peptides that set in motion the evolution of life into more complex forms.

Investigating the question as to how life could emerge long ago on the early Earth is one of the most fascinating challenges for science. Which conditions must have prevailed for the basic building blocks of more complex life to form? One of the main answers is based upon the so-called RNA world idea, which molecular biology pioneer Walter Gilbert formulated in 1986. The hypothesis holds that nucleotides—the basic building blocks of the nucleic acids A, C, G, and U—emerged out of the primordial soup, and that short RNA molecules then formed out of the nucleotides. These so-called oligonucleotides were already capable of encoding small amounts of genetic information.

As such single-stranded RNA molecules could also combine into double strands, however, this gave rise to the theoretical possibility that the molecules could replicate themselves—i.e. reproduce. Only two nucleotides fit together in each case, meaning that one strand is the exact counterpart of another and thus forms the template for another strand.

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Dr. Thomas Lehner was tired of his research repeatedly hitting a wall.

A scientist at the National Institute of Mental Health, Lehner studies the genetic underpinnings of neuropsychiatric disorders. Teasing out associated genes turned out to be relatively simple. Schizophrenia, for example, is linked to small variations in some 360 genes.

The problem is identifying the ones that really matter—culprit gene variants that can be turned into predictive tests, similar to the BRCA gene for breast cancer.

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Circa 2017

Schizophrenia is a genetically related mental illness, in which the majority of genetic alterations occur in the non-coding regions of the human genome. In the past decade, a growing number of regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) have been identified to be strongly associated with schizophrenia. However, the studies of these ncRNAs in the pathophysiology of schizophrenia and the reverting of their genetic defects in restoration of the normal phenotype have been hampered by insufficient technology to manipulate these ncRNA genes effectively as well as a lack of appropriate animal models. Most recently, a revolutionary gene editing technology known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated nuclease 9 (Cas9; CRISPR/Cas9) has been developed that enable researchers to overcome these challenges. In this review article, we mainly focus on the schizophrenia-related ncRNAs and the use of CRISPR/Cas9-mediated editing on the non-coding regions of the genomic DNA in proving causal relationship between the genetic defects and the pathophysiology of schizophrenia. We subsequently discuss the potential of translating this advanced technology into a clinical therapy for schizophrenia, although the CRISPR/Cas9 technology is currently still in its infancy and immature to put into use in the treatment of diseases. Furthermore, we suggest strategies to accelerate the pace from the bench to the bedside. This review describes the application of the powerful and feasible CRISPR/Cas9 technology to manipulate schizophrenia-associated ncRNA genes. This technology could help researchers tackle this complex health problem and perhaps other genetically related mental disorders due to the overlapping genetic alterations of schizophrenia with other mental illnesses.

Keywords: CRISPR/Cas9; gene editing; lncRNAs; miRNAs; non-coding RNAs; schizophrenia.

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When cells reproduce, the internal mechanisms that copy DNA get it right nearly every time. Rice University bioscientists have uncovered a tiny detail that helps understand how the process could go wrong.

Their study of enzymes revealed the presence of a central metal ion critical to DNA replication also appears to be implicated in misincorporation, the faulty ordering of nucleotides on new strands.

The observation reported in Nature Communications could help find treatments for and the diseases they cause, including cancer.

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CRISPR-Cas9 is considered a revolutionary gene editing tool, but its applications are limited by a lack of methods by which it can be safely and efficiently delivered into cells. Recently, a research team from Kumamoto University, Japan, have constructed a highly flexible CRISPR-Cas9 carrier using aminated polyrotaxane (PRX) that can not only bind with the unusual structure of Cas9 and carry it into cells, but can also protect it from intracellular degradation by endosomes.

Clustered regularly interspaced short palindromic repeats (CRISPR) and their accompanying protein, CRISPR-associated protein 9 (Cas9), made international headlines a few years ago as a game-changing genome editing system. Consisting of Cas9 and strand of genetic material known as a single-guide RNA (sgRNA), the system can target specific regions of DNA and function as “molecular scissors” to make precise edits. The direct delivery of Cas9–sgRNA complexes, i.e. Cas9 ribonucleoproteins (RNPs), into the nucleus of the cell is considered the safest and most efficient way to achieve genome editing. However, the Cas9 RNP has poor cellular permeability, and thus requires a carrier molecule to transport it past the first hurdle of the cell membrane before it can get to the cell nucleus. These carriers need to bind with Cas9 RNP, carry it into the cell, prevent its degradation by intracellular organelles called “endosomes,” and finally release it without causing any changes to its structure.

In a recent paper published in the June 2022, Volume 27 of Applied Materials Today, a research team from Kumamoto University has developed a transformable polyrotaxane (PRX) carrier that can facilitate genome editing using Cas9RNP with high efficiency and usability. “While there have been some PRX-based drug carriers for and proteins reported before, this is the first report on PRX-based Cas9 RNP carrier. Moreover, our findings describe how to precisely control intracellular dynamics across multiple steps. This will prove invaluable for future research in this direction,” says Professor Keiichi Motoyama, a corresponding author of the paper.

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