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Category: genetics

MicroRNAs as Biomarkers in Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA. Currently, there is a lack of reliable biomarkers to monitor SMA; therefore, the search for novel SMA biomarkers, including miRNAs, is crucial as reliable tools are needed to track disease progression, predict the response to therapy and understand the different clinical outcomes of available treatments.

Weird rings of DNA fuel cancers. This scientist leads the effort to target them

Scientist Paul Mischel is championing the importance of odd rings of DNA in tumors—and their promise as targets for cancer therapy.

Learn more on DNADay.

Paul Mischel and others are testing therapies for rogue genetic loops that drive tumor evolution and growth.

Re-engineered human cells boost gene-editing particle potency across multiple delivery systems

Gene editing has emerged as a powerful approach for targeting the genetic causes of disease, but getting the editing machinery into the right cells efficiently, safely, and at the scale needed for therapies remains one of the biggest set of challenges in the field.

Among the leading delivery vehicles are engineered virus-like particles, which resemble viruses—and share their knack for entering human cells—but carry no viral genes. Scientists load them with gene editing tools and use them to make precise changes in targeted cells.

Most efforts to improve these particles have focused on redesigning the particles themselves. A new study led by Valhalla Fellow at Whitehead Institute, Aditya Raguram and lab technician Diana Ly, focuses instead on the human cells that produce them.

The Immune System Impacts Longevity: What To Measure

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How parasites exit host cells

After infecting host cells and reproducing, the parasite life cycle requires them to egress so that they can move to the next host. Past studies on the genes required for this process have been conducted but show conflicting results.

The methodology of past studies often involved opening the host cells during the screening process. Consequently, researchers were unable to reliably identify when mutations prevent parasites from egressing.

To avoid the same limitations, the team used an in vivo approach to screen for essential genes instead.

“Our in vivo screen, based on CRISPR, identified for the first time that the MIC11 gene is essential for host cell membrane permeabilization and parasite egress.” Explains the lead author.

Further tests demonstrated that deleting the MIC11 gene led the parasites to be unable to rupture the host cell membrane. By incapacitating parasites in this way, they could no longer exit the host cells, majorly disrupting the parasite life cycle.

“We also found evidence that MIC11 interacts with PLP1, providing further evidence of MIC11’s crucial role,” explains the senior author. “PLP1 is another parasite protein that was already known to be essential for egress.” ScienceMission sciencenewshighlights.

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Frontiers: Year 2020 this gene therapy in mice shows promise for als gene therapy in humans

Gene therapy is an emerging and powerful therapeutic tool to deliver functional genetic material to cells in order to correct a defective gene. During the past decades, several studies have demonstrated the potential of AAV-based gene therapies for the treatment of neurodegenerative diseases. While some clinical studies have failed to demonstrate therapeutic efficacy, the use of AAV as a delivery tool has demonstrated to be safe. Here, we discuss the past, current and future perspectives of gene therapies for neurodegenerative diseases. We also discuss the current advances on the newly emerging RNAi-based gene therapies which has been widely studied in preclinical model and recently also made it to the clinic.

Gene therapy is an emerging therapeutic tool used to deliver functional genetic material to cells in order to correct a defective gene. By delivering a copy of a therapeutic gene to affected cells, the product encoded by that gene [i.e., its messenger RNA (mRNA) and/or proteins] will be continuously synthesized within the cell, utilizing the cell’s own transcriptional and translational machinery (Porada et al., 2013). The main advantage of this technology is that it offers a potentially life-long therapeutic effect without the need for repeated administration. Gene therapy can be used to correct defective genes by introducing a functional copy of the gene, by silencing a mutant allele using RNA interference (RNAi), by introducing a disease-modifying gene, or by using gene-editing technology (Grimm and Kay, 2007; Dow et al., 2015; Saraiva et al., 2016).

Gene therapy vectors can be either viral or non-viral. Different physical and chemical systems can be applied to deliver therapeutic genes to cells without the need of a viral vector. Non-viral vectors have no size limitation for the therapeutic gene, generally have a low immunogenicity risk, and can be produced at relatively low costs (Nayerossadat et al., 2012). However, due to the fact that high therapeutic doses are required when using non-viral technologies, and the resulting gene expression is generally transient, most gene therapies now rely on viral vectors. Numerous viral vector types have been tested in clinic, including vaccinia, measles, vesicular stomatitis virus (VSV), polio, reovirus, adenovirus, lentivirus, γ-retrovirus, herpes simplex virus (HSV) and adeno-associated virus (AAV) (Lundstrom, 2018).

Gene therapy for deafness approved

The world’s first gene therapy for deafness received approval from the U.S. Food and Drug Administration today. The treatment, from biotech company Regeneron, targets hearing loss caused by inherited mutations in the OTOF gene, which encodes otoferlin, a protein that allows the inner ear’s hair cells to sense and transmit sound to the brain. Patients receive a one-time ear injection containing viral vectors that carry a working copy of the OTOF gene into their cells. In a clinical trial, nine of 12 deaf children who initially received the Regeneron therapy gained enough hearing to stop using cochlear implants; three within that group ended up having normal hearing. Although many gene therapies cost $1 million or more, Regeneron said its treatment, called Otarmeni, will be free in the United States.

Eli Lilly & Co. and researchers in China are also developing gene therapies for OTOF mutations, which account for up to 3% of cases of inherited deafness. One U.S.-Chinese team reported in Nature this week that among 24 patients, including some adults, hearing improvements have lasted more than 2 years in some cases, NPR reports. Researchers eventually hope to treat other types of genetic deafness as well, but those attempts face more challenges. For example, for some disorders, it may be necessary to regenerate lost hair cells. In others, targeting the wrong cell type could damage hearing.

For the first time, scientists pinpoint the brain cells behind depression

Scientists have identified two specific types of brain cells that behave differently in people with depression, offering a clearer picture of what is happening inside the brain. By analyzing donated brain tissue with advanced genetic tools, the researchers found changes in neurons linked to mood and stress, as well as in immune-related microglia cells. These differences point to disruptions in key brain systems and reinforce that depression is rooted in biology, not just emotions.

Gene-screen strategy separates Parkinson’s promoters from protectors, revealing new drug targets

A novel strategy that combines computational and experimental approaches has allowed researchers at Baylor College of Medicine and the Duncan Neurological Research Institute (Duncan NRI) at Texas Children’s Hospital to distinguish alterations in gene function that contribute to Parkinson’s disease from those that protect from the condition. The study, published in Neurobiology of Disease, revealed novel risk factors and previously unrecognized therapeutic targets, offering hope for a future in which effective therapies will be available to prevent, slow down or stop this devastating disease.

“Parkinson’s disease is the most common neurodegenerative movement disorder—it affects more than 10 million people worldwide,” said corresponding author Dr. Juan Botas, professor of molecular and human genetics and molecular and cellular biology at Baylor. Botas also is a member of the Duncan NRI and director of the High Throughput Behavioral Screening Core at Texas Children’s.

“People with the condition have tremors, muscle stiffness and balance problems. They move slowly with a shuffling gait; their symptoms often start gradually and worsen over the years. Current therapies only relieve symptoms but do not prevent the gradual loss of brain cells called neurons that cause the disease,” said Dr. Botas.

Hidden mosquito viruses emerge as RNA immune signals map global infections

Aedes aegypti, commonly known as the yellow fever mosquito, is a highly adapted, invasive mosquito species recognized as a major global health threat that acts as the primary vector for several severe diseases, most notably dengue fever, as well as yellow fever, chikungunya and Zika virus. Local government agencies conduct routine molecular surveillance of these mosquitoes to detect and track viruses. However, they are primarily limited to using conventional reverse transcription polymerase chain reaction methodologies, which can only detect known pathogens that have already been identified and for which specific genetic primers have been developed.

Recent research efforts applying high-throughput RNA sequencing have led to a large expansion in the mosquito virome (the entire collection of viruses contained within mosquitoes). However, questions remain as to how persistent insect viruses are within mosquito colonies, how insect viruses interact with mosquito immune responses and how frequently insect viruses can be transmitted.

A new study by Boston University Chobanian & Avedisian School of Medicine researchers looked at the mosquitoes’ immune response to discover many more insect viruses and they hope to someday use the mosquitoes’ own immune system to battle some of the most pervasive and antagonistic human viruses. The findings are published in the journal Nature Communications.

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