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A recent study published in Nature Genetics identified 10 new genetic regions associated with Brugada syndrome, a cardiac arrhythmia disorder associated with sudden death in young adults.

The findings expand possibilities for predictive risk scoring and provide new targets for therapeutic study, according to Alfred George, Jr., MD, chair and the Alfred Newton Richards Professor of Pharmacology and a co-author of the study.

“Prior to this work, there were only two genomic regions associated with Brugada syndrome risk that were identified by genome-wide studies. Data from the new study greatly expands this to 12 regions with a total of 21 genetic signals to better explain risk for Brugada syndrome,” George said. “The results also provide the basis for a polygenic risk score that can be used to assess risk in individuals.”

Scientists at Northwestern Medicine are using new advances in CRISPR gene-editing technology to uncover new biology that could lead to longer-lasting treatments and new therapeutic strategies for Human Immunodeficiency Virus (HIV).

The HIV epidemic has been overlooked during the COVID-19 pandemic but represents a critical and ongoing threat to human health with an estimated 1.5 million new infections in the last year alone.

Drug developers and research teams have been searching for cures and new treatment modalities for HIV for over 40 years but are limited by their understanding of how the virus establishes infection in the human body. How does this small, unassuming virus with only 12 proteins—and a genome only a third of the size of SARS-CoV-2—hijack the body’s cells to replicate and spread across systems?

Further study of newly-sequenced portions of the genome could also help scientists better understand how humans evolved particular traits, such as the bigger brains that sent them down a genetically distinct path from their great ape ancestors.

“The things that make our frontal cortex bigger come from the genes that map in these repetitive regions,” said Evan Eichler, a professor in the department of genome sciences at the University of Washington School of Medicine and also part of the research collaborative.

Advances in genomic sequencing technology could drive a renaissance of medical breakthroughs, the researchers say.

Scientists have managed to safely reverse the signs of aging in mice by genetically reprogramming some of their cells.

GABAergic dysfunctions have been implicated in the pathogenesis of schizophrenia, especially the associated cognitive impairments. The GABA synthetic enzyme glutamate decarboxylase 67-kDa isoform (GAD67) encoded by the GAD1 gene is downregulated in the brains of patients with schizophrenia. Furthermore, a patient with schizophrenia harboring a homozygous mutation of GAD1 has recently been discovered. However, it remains unclear whether loss of function of GAD1 leads to the symptoms observed in schizophrenia, including cognitive impairment. One of the obstacles faced in experimental studies to address this issue is the perinatal lethality of Gad1 knockout (KO) mice, which precluded characterization at the adult stage. In the present study, we successfully generated Gad1 KO rats using CRISPR/Cas9 genome editing technology.

Type 1 diabetes is caused by insulin deficiency resulting from immune-mediated destruction of pancreatic beta cells. Its cause is multifactorial, with complex genetic factors and a strong influence of certain HLA types that probably indicates T-cell-mediated disease.1 Despite attempts to halt the autoimmune destruction of the pancreatic islet at disease onset with immunotherapeutic approaches, 1 recovery of pancreatic beta-cell function remains a challenge because type 1 diabetes is not reversible, even early in the disease.

Correspondence from The New England Journal of Medicine — STAT1 Gain of Function, Type 1 Diabetes, and Reversal with JAK Inhibition.

Circa 2017 😀

As the most common subtype of Leber congenital amaurosis (LCA), LCA10 is a severe retinal dystrophy caused by mutations in the CEP290 gene. The most frequent mutation found in patients with LCA10 is a deep intronic mutation in CEP290 that generates a cryptic splice donor site. The large size of the CEP290 gene prevents its use in adeno-associated virus (AAV)-mediated gene augmentation therapy. Here, we show that targeted genomic deletion using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system represents a promising therapeutic approach for the treatment of patients with LCA10 bearing the CEP290 splice mutation. We generated a cellular model of LCA10 by introducing the CEP290 splice mutation into 293FT cells and we showed that guide RNA pairs coupled with SpCas9 were highly efficient at removing the intronic splice mutation and restoring the expression of wild-type CEP290. In addition, we demonstrated that a dual AAV system could effectively delete an intronic fragment of the Cep290 gene in the mouse retina. To minimize the immune response to prolonged expression of SpCas9, we developed a self-limiting CRISPR/Cas9 system that minimizes the duration of SpCas9 expression. These results support further studies to determine the therapeutic potential of CRISPR/Cas9-based strategies for the treatment of patients with LCA10.

Keywords: CEP290; CRISPR/Cas9; LCA10.

Continue reading “CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10” »

University of Notre Dame researchers have discovered another way tumor cells transfer genetic material to other cells in their microenvironment, causing cancer to spread.

In their latest study, published in Cell Reports, Crislyn D’Souza-Schorey, the Morris Pollard Professor in the Department of Biological Sciences, and collaborators discovered that DNA “cargo” is transported in small informational sacs called extracellular microvesicles. Their study is a continuation of work her lab has undertaken to further understand the sharing of information between cells.

“We’ve shown that DNA present in these microvesicles is related to metastasis, so now we have a great platform to assess for genetic aberrations,” said D’Souza-Schorey, who is also affiliated with the Berthiaume Institute for Precision Health, the Boler-Parseghian Center for Rare and Neglected Diseases and the Harper Cancer Research Institute.

Scientists at La Jolla Institute for Immunology (LJI) have found that people with Parkinson’s disease have a clear “genetic signature” of the disease in their memory T cells. The scientists hope that targeting these genes may open the door to new Parkinson’s treatments and diagnostics.