Lifeboat Foundation

An ex vivo gene-edited cell therapy for sickle cell disease (SCD) being developed by Sangamo Therapeutics and Sanofi has generated positive early Phase I/II results in three patients—data that persuaded a committee of the European Medicines Agency (EMA) to support an orphan designation for the drug candidate.

The EMA’s Committee for Orphan Medicinal Products (COMP) has adopted a positive opinion for the orphan designation for BIVV003 (autologous CD34+ hematopoietic stem and progenitor cells transfected with zinc finger nuclease mRNAs SB-mRENH1 and SB-mRENH2) following its meeting of January 19–21— minutes of which were posted this month on the EMA’s website.

COMP based its recommendation on data showing that the first three patients with sickle cell disease ended up “without recurrence of previous SCD symptoms” following treatment with BIVV003 in the Phase I/II PRECIZN-1 trial (NCT03653247).

Using an improved version of the gene editing tool CRISPR/Cas9, researchers knocked out up to twelve genes in plants in a single blow. Until now, this had only been possible for single or small groups of genes. The approach was developed by researchers at Martin Luther University Halle-Wittenberg (MLU) and the Leibniz Institute of Plant Biochemistry (IPB). The method makes it easier to investigate the interaction of various genes. The study appeared in The Plant Journal.

The inheritance of traits in plants is rarely as simple and straightforward as Gregor Mendel described. The monk, whose experiments in the 19th century on trait inheritance in peas laid the foundation of genetics, in fact got lucky. “In the traits that Mendel studied, the rule that only one gene determines a specific trait, for example the color of the peas, happened to apply,” says plant geneticist Dr. Johannes Stuttmann from the Institute of Biology at MLU. According to the researcher, things are often much more complicated. Frequently there are different genes that, through their interaction with one another, result in certain traits or they are partly redundant, in other words they result in the same trait. In this case, when only one of these genes is switched off, the effects are not visible in the plants.

The scientists at MLU and IPB have now developed a way to study this complex phenomenon in a more targeted way by improving CRISPR/Cas9. These gene editing tools can be used to cut the DNA of organisms at specific sites. The team built on the work of biologist Dr. Sylvestre Marillonnet who developed an optimized building block for the CRISPR/Cas9 system at the IPB. “This building block helps to produce significantly more Cas9 enzyme in the plants, which acts as a scissor for the genetic material,” explains Stuttmann. The researchers added up to 24 different guide RNAs which guide the scissor enzyme to the desired locations in the genetic material. Experiments on thale cress (Arabidopsis thaliana) and the wild tobacco plant Nicotiana benthamiana proved that the approach works. Up to eight genes could be switched off simultaneously in the tobacco plants while, in the thale cress, up to twelve genes could be switched off in some cases.

In the case of DMD caused by a duplication mutation, CRISPR can simply snip away the harmful duplicate gene, which is much simpler than delivering a new gene or replacing the old.

For the first time in a live animal, researchers have successfully reversed a gene mutation, called a “duplication mutation,” by gene editing.

“The results were surprising, but convincing, says Yannick Pauchet, a molecular entomologist also at the Max Planck Institute for Chemical Ecology. ” According to the data they provide, horizontal gene transfer is the most parsimonious explanation,” he says.

But how the whitefly managed to swipe a plant gene is unclear. One possibility, says Turlings, is that a virus served as an intermediate, shuttling genetic material from a plant into the whitefly genome.

As researchers s… See More.

Continue reading “First known gene transfer from plant to insect identified” »

(From left) Expedition 65 crew members Pyotr Dubrov, Oleg Novitskiy and Mark Vande Hei, pose for a photo during Soyuz qualification exams in Moscow.

The Expedition 64 crew continued researching how microgravity affects biology aboard the International Space Station today. The orbital residents also conducted vein and eye checks and prepared for three new crew members due in early April.

NASA Flight Engineer Shannon Walker joined Russian cosmonauts Sergey Ryzhikov and Sergey Kud-Sverchkov for vein and eye scans on Thursday. Japan Aerospace Exploration Agency astronaut Soichi Noguchi led the effort scanning veins in the trio’s neck, clavicle and shoulder areas using the Ultrasound 2 device in the morning. In the afternoon, Noguchi examined Walker’s eyes using the orbiting lab’s optical coherence tomography gear.

Continue reading “Vein, Eye Scans on Station as Next Crew Nears Launch” »

The research team, led by Todd Lencz, PhD, with Itsik Pe’er, PhD, Tom Maniatis, PhD, and Erin Flaherty, PhD, of Columbia University, carried out a genetic study identifying a single letter change in the DNA code in the PCDHA3 gene that is associated with schizophrenia. The affected gene makes a type of protein called a protocadherin, which generates a cell surface “barcode” required for neurons to recognize, and communicate with, other neurons. They found that the PCDHA3 variant blocks this normal protocadherin function.

The discovery was made possible by the special genetic characteristics of the samples studied by Lencz’s team—patients with schizophrenia and healthy volunteers drawn from the Ashkenazi Jewish population. The Ashkenazi Jewish population represents an important population for study based on its unique history. Just a few hundred individuals who migrated to Eastern Europe less than 1000 years ago are the ancestors of nearly 10 million Ashkenazi Jews today. This lineage, combined with a tradition of marriage within the community, has resulted in a more uniform genetic background in which to identify disease-related variants.

“In addition to our primary findings regarding PCDHA3 and related genes, we were able— due to the unique characteristics of the Ashkenazi population—to replicate several prior findings in schizophrenia despite relatively small sample sizes,” said Lencz, professor in the Institute of Behavioral Science at the Feinstein Institutes. “In our study, we demonstrated this population represents a smart, cost-effective strategy for identifying disease-related genes. Our findings allow us to zero in on a novel aspect of brain development and function in our quest to develop new treatments for schizophrenia.”

It is well established that rare, damaging genetic variants with strong effects contribute to autism. Although individually rare, these variants are collectively common: Clinical genetic testing identifies them in at least 25 percent of autistic people. Studies of these variants have implicated more than 100 genes — and counting — in autism.

Identifying these genes is important — not only for clinical care, but also for advancing our understanding of the neural circuits and processes involved in autism or in its core traits. It creates the opportunity to develop therapies targeted to specific molecular diagnoses. And as we learn more about these genes and the consequences of variants that disrupt their function, we have the potential to better understand the mechanisms underlying cases of autism in which a definitive genetic diagnosis cannot yet be made.

But the genetic findings in people with autism are not unique; deleterious variants in the same genes are also implicated in other neurodevelopmental conditions, such as intellectual disability, epilepsy, attention deficit hyperactivity disorder and schizophrenia. Specific genes and variants do not map neatly onto categorical clinical diagnoses or the core cognitive and behavioral traits that define them. In fact, there is not yet a single example of a gene that, when mutated, increases the likelihood of autism but not of other neurodevelopmental conditions.

Long but annotated! Most important here is human data for specific treatments due out starting in May or June. And apparently they had a mouse study where they expected a paper due out already but other groups chimed in to help with more testing so there is a delay.

Liz Parrish, CEO of BioViva Science and patient zero of biological rejuvenation with gene therapies, is interviewed by Zora Benhamou on her fresh podcast “HackMyAge”.

Continue reading “Liz Parrish goes deep into gene therapies at the HackMyAge Podcast by Zora (March 2021)” »

Summary: A new genetic engineering strategy significantly reduces levels of tau in animal models of Alzheimer’s disease. The treatment, which involves a single injection, appears to have long-last effects.

Source: Mass General.

Researchers have used a genetic engineering strategy to dramatically reduce levels of tau–a key protein that accumulates and becomes tangled in the brain during the development of Alzheimer’s disease–in an animal model of the condition.