Animal Models - GEG Tech top picks

The genetically modified organs seemed to function for more than two days but some researchers are sceptical that the experiments had value.

Tumor suppressor genes block cell growth, preventing cancer cells from spreading. Scientists believe that mutations in these genes allow tumors to flourish unchecked. Now, Howard Hughes Medical Institute researcher Stephen Elledge's team has discovered a surprising new action for many of these faulty genes. Elledge had a hunch that defective tumor suppressor genes were doing something more than speeding up tumor cell growth. From a list of 7,500 genes, her team used CRISPR to engineer thousands of tumor cells. Each was missing a functional version of one of these genes. The researchers placed the cells in two types of mice: those with an immune system and those without. Then the team studied the tumors that developed. Elledge's method revealed the many different genes that tumors can mutate to evade the body's defenses. To explore the possible mechanisms triggered by the mutations, the researchers focused on a gene called GNA13. The gene's mutation protects cancer cells from the immune system's T cells, creating a safe space for the tumor to grow.

According to the study, more than 100 mutated tumor suppressor genes can prevent the immune system from identifying and destroying malignant cells in mice.

Swiss pharmaceutical company Novartis launched a lottery-style program to give away doses of its pricey gene therapy for free, drawing criticism from patient groups.

Australia has approved the use of CRISPR gene editing tool on plants and animals without the oversight of a governmental body. The controversial move has been called a 'middle ground' compared to regulations on other countries.

Police to investigate He Jiankui after last year’s claim to have altered the DNA of twin girls

For the first time, scientists have performed prenatal gene editing to prevent a lethal metabolic disorder in laboratory animals, offering the potential to treat human congenital diseases before birth. Published today in Nature Medicine, research from Children’s Hospital of Philadelphia (CHOP) and the Perelman School of Medicine at the University of Pennsylvania offers proof-of-concept for prenatal use of a sophisticated, low-toxicity tool that efficiently edits DNA building blocks in disease-causing genes.

OHSU scientists have discovered a naturally occurring disease in monkeys that mimics a deadly childhood neurodegenerative disorder in people – a finding that holds promise for developing new gene therapies to treat Batten disease.

Transplanting engineered neural cells into the brain of an amyotrophic lateral sclerosis (ALS) animal model delayed disease progression and extended the animals’ survival, a study shows.

In the present study, the CRISPR/Cas system was used to target the Tph2 gene in Bama mini pig fetal fibroblasts. It was found that CRISPR/Cas9 targeting efficiency could be as high as 61.5%, and the biallelic mutation efficiency reached at 38.5%. The biallelic modified colonies were used as donors for somatic cell nuclear transfer (SCNT) and 10 Tph2 targeted piglets were successfully generated. These Tph2 KO piglets were viable and appeared normal at the birth. However, their central 5-HT levels were dramatically reduced, and their survival and growth rates were impaired before weaning. These Tph2 KO pigs are valuable large-animal models for studies of 5-HT deficiency induced behavior abnomality.

Here, the scientists describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo. 

With over a hundred thousand people waiting for an organ transplant in the US alone, scientists are racing to find options besides human donors. Now for the first time, a pig kidney has been successfully transplanted into a person.

The combination of several genetic errors leads to the development of cancer and many other diseases based on genetic abnormalities. The 3Cs multiplex technique based on CRISPR-CAS technology developed at the Frankfurt Goethe University now offers the possibility to simulate combinations of millions of genetic defects and to study their effects in cell culture. Scientists at the Institute for Biochemistry II at Goethe University have enhanced the 3Cs technique which they developed and patented three years ago. 3Cs stands for covalent-closed circular-synthesized, because of the RNA parts used for CRISPR-CAS are produced with the help of a circular synthesis and are thus distributed more uniformly. With an entire library of such RNA rings, any gene in a cell can be specially addressed to change or cut it. The new 3Cs multiplex technique now even allows the simultaneous manipulation of two genes in one cell. This technique thus makes it possible to search very efficiently in cell culture experiments for genes that play a major role in cancer, and also in diseases of the nervous and immune systems, and that could be the potential target of certain treatments. certain treatments.

Pig-primate chimeras have been born live for the first time but died within a week. The two piglets, created by a team in China, looked normal although a small proportion of their cells were derived from cynomolgus monkeys.

“This is the first report of full-term pig-monkey chimeras,” says Tang Hai at the State Key Laboratory of Stem Cell and Reproductive Biology in Beijing.

Read more: https://link.springer.com/article/10.1007%2Fs13238-019-00676-8

Biologists have embraced CRISPR’s ability to quickly and cheaply modify the genomes of popular model organisms, such as mice, fruit flies and monkeys. Now they are trying the tool on more-exotic species, many of which have never been reared in a lab or had their genomes analysed. “We finally are ready to start expanding what we call a model organism,” says Tessa Montague, a molecular biologist at Columbia University in New York City. 

But the practical challenges of breeding and maintaining unconventional lab animals persist.

Researchers have developed a comprehensive way to evaluate how immune responses of humanized mice measure up to actual humans.

 Findings from the new study were published recently in Nature Communications through an article titled “Selective expansion of myeloid and NK cells in humanized mice yields human-like vaccine responses.”

On Wednesday, researchers from University of Texas Medical Branch published a new paper in the journal Science Translational Medicine.

In it, they detail their latest milestone along the path to creating lab-grown lungs for humans: they can now successfully transplant these bioengineered lungs into pigs.

Knock-in mice with precise insertions are efficiently generated through delivery of CRISPR–Cas9 to two-cell embryos.

Researchers from Columbia University found in 2017 that Crispr can cause genetic mutations and they have now been forced to accept their study was wrong and Crispr is harmless.

The present work demonstrates that multiplex embryo transfer and multiplex gene targeting can be used to quickly and efficiently generate mutant rabbit founders. Four lines of SGM (e.g. FOXN1, RAG2, IL2RG, and PRKDC) immunodeficient rabbits, as well as multigenic mutant immunodeficient rabbits have been produced. These animals may prove useful for biomedical research.

Xenotransplantation is a promising strategy to alleviate the shortage of organs for human transplantation.

Here, the scientists confirmed the risk of cross-species transmission of porcine endogenous retroviruses (PERVs), and observed the horizontal transfer of PERVs among human cells. Using CRISPR-Cas9, they inactivated all the PERVs in a porcine primary cell line and generated PERV-inactivated pigs via somatic cell nuclear transfer. This study highlighted the value of PERV inactivation to prevent cross-species viral transmission and demonstrated the successful production of PERV-inactivated animals to address the safety concern in clinical xenotransplantation.