Researchers find a new method for gene therapy, ‘delete-to-recruit’, and show its potential for treating sickle cell disease and thalassemia.
Category: biotech/medical – Page 9
AI-Validated Brain Targeted mRNA Lipid Nanoparticles with Neuronal TropismClick to copy article linkArticle link copied!
Targeting therapeutic nanoparticles to the brain poses a challenge due to the restrictive nature of the blood–brain barrier (BBB). Here we report the development of mRNA-loaded lipid nanoparticles (LNPs) functionalized with BBB-interacting small molecules, thereby enhancing brain delivery and gene expression. Screening brain-targeted mRNA-LNPs in central nervous system (CNS) in vitro models and through intravenous administration in mice demonstrated that acetylcholine-conjugated LNPs achieved superior brain tropism and gene expression, outperforming LNP modifications with nicotine, glucose, memantine, cocaine, tryptophan, and other small molecules. An artificial intelligence (AI)-based model designed to predict the BBB permeability of small-molecule ligands showed strong alignment with our experimental results, providing in vivo validation of its predictive capacity. Cell-specific biodistribution analysis in Cre-reporter Ai9 mice showed that acetylcholine-functionalized LNPs preferentially transfected neurons and astrocytes following either intravenous or intracerebral administration. Mechanistic studies suggest that acetylcholine-LNP uptake is mediated by the functional engagement of acetylcholine receptors (AchRs) followed by endocytosis, which synergistically enhances intracellular mRNA delivery. Moreover, acetylcholine-LNPs successfully crossed a human BBB-on-a-chip model, enabling transgene expression in human iPSC-derived neurons. Their effective penetration and transfection in human brain organoids further support their potential activity in human-based systems. These findings establish a predictive and modular framework for engineering CNS-targeted LNPs, advancing precision gene delivery for brain disorders.
Largest genetic study to date identifies 13 new DNA regions linked to dyslexia
Dyslexia is a neurodevelopmental condition estimated to affect between 5–10% of people living in most countries, irrespective of their educational and cultural background. Dyslexic individuals experience persistent difficulties with reading and writing, often struggling to identify words and spell them correctly.
Past studies with twins suggest that dyslexia is in great part heritable, meaning that its emergence is partly influenced by genetic factors inherited from parents and grandparents. However, the exact genetic variants (i.e., small differences in DNA sequences) linked to dyslexia have not yet been clearly delineated.
Researchers at University of Edinburgh, the Max Planck Institute for Psycholinguistics and various other institutes recently carried out the largest genome-wide association study to date exploring the genetic underpinnings of dyslexia. Their paper, published in Translational Psychiatry, identifies several previously unknown genetic loci that were found to be linked to an increased likelihood of experiencing dyslexia.
Dormant no more: Brain protein’s hidden role may reshape psychiatric and neurological treatments
In a new research report, scientists at Johns Hopkins Medicine say they have identified a potential target for drugs that could dial up or down the activity of certain brain proteins in efforts to treat psychiatric disorders, such as anxiety and schizophrenia, and a neurological condition that affects movement.
The proteins, called delta-type ionotropic glutamate receptors, or GluDs, have long been understood to play a major role in signaling between neurons. Mutations in GluD proteins are thought to drive psychiatric conditions, including anxiety and schizophrenia, the scientists say. Yet, scientists had few clues as to how GluDs function, hampering the ability to find treatments to regulate them.
“This class of protein has long been thought to be sitting dormant in the brain,” says Edward Twomey, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine. “Our findings indicate they are very much active and offer a potential channel to develop new therapies.”
‘Drop-printing’ shows potential for constructing bioelectronic interfaces that conform to complex surfaces
With the rapid development of wearable electronics, neurorehabilitation, and brain-machine interfaces in recent years, there has been an urgent need for methods to conformally wrap thin-film electronic devices onto biological tissues to enable precise acquisition and regulation of physiological signals.
Conventional methods typically rely on external pressure to force devices onto conformal contact. However, when applied to uneven three-dimensional surfaces such as skin, brain, or nerves, they generate significant internal stress which can easily damage fragile metal circuits and inorganic chips. This is an obstacle to the advancement of flexible electronics.
In a study published in Science, Prof. Song Yanlin’s team from the Institute of Chemistry of the Chinese Academy of Sciences, along with collaborators from Beijing Tiantan Hospital, Nanyang Technological University, and Tianjin University, propose a new film transfer strategy named as drop-printing, which has potential applications in bioelectronics, flexible displays, and micro-/nano-manufacturing.
Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities
T cells can be reprogrammed with transgenic antigen recognition receptors, including chimeric antigen receptors and T cell receptors, to selectively recognize and kill cancer cells. Such adoptive T cell therapies are effective in patients with certain haematological cancers but challenges persist, including primary and secondary resistance, a lack of efficacy in patients with solid tumours, a narrow range of targetable antigens, and time-consuming and complex manufacturing processes. CRISPR-based genome editing is a potent strategy to enhance cellular immunotherapies. Conventional CRISPR–Cas9 systems are useful for gene editing, transgene knock-in or gene knockout but can result in undesired editing outcomes, including translocations and chromosomal truncations. Base editing and prime editing technologies constitute a new generation of CRISPR platforms and enable highly precise and programmable installation of defined nucleotide variants in primary T cells. Owing to their high precision and versatility, base editing and prime editing systems, hereafter collectively referred to as CRISPR 2.0, are advancing to become the new standard for precision-engineering of cellular immunotherapies. CRISPR 2.0 can be used to augment immune cell function, broaden the spectrum of targetable antigens and facilitate streamlined production of T cell therapies. Notably, CRISPR 2.0 is reaching clinical maturity, with multiple clinical trials of CRISPR 2.0-modified cellular therapies currently ongoing. In this Review, we discuss emerging CRISPR 2.0 technologies and their progress towards clinical translation, highlighting challenges and opportunities, and describe strategies for the use of CRISPR 2.0 to advance cellular immunotherapy for haematological malignancies and solid tumours in the future.
#CRISPR9
Several persistent challenges limit the efficacy and applicability of adoptive T cell therapies for cancer, including suboptimal function and/or persistence in vivo, a narrow range of targetable antigens and complex manufacturing processes. This Review discusses the potential of ‘CRISPR 2.0’ precision gene-editing platforms, such as base editing and prime editing to address all of these challenges, and describes the progress made towards clinical translation of these technologies.
Lab-grown human brain tissue directs butterfly simulation
Could organoid-driven computing be the future of AI power?
This deadly brain disorder can develop a decade after you get the measles — and it just killed a child
A school-aged child in L.A. recently died after developing a rare neurological disease years after contracting the measles.
Authorities didn’t reveal many details about the case, except that the child was infected with measles as an infant, before they were eligible for the vaccine.
Measles is a respiratory disease that spreads easily from person to person. The first dose of the measles, mumps and rubella (MMR) vaccine is routinely recommended for kids between 12 and 15 months old. A second dose is given before kindergarten or first grade.
The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection
Regular exercise is associated with pronounced health benefits. The molecular processes involved in physiological adaptations to exercise are best understood in skeletal muscle. Enhanced mitochondrial functions in muscle are central to exercise-induced adaptations. However, regular exercise also benefits the brain and is a major protective factor against neurodegenerative diseases, such as the most common age-related form of dementia, Alzheimer’s disease, or the most common neurodegenerative motor disorder, Parkinson’s disease. While there is evidence that exercise induces signalling from skeletal muscle to the brain, the mechanistic understanding of the crosstalk along the muscle–brain axis is incompletely understood. Mitochondria in both organs, however, seem to be central players.
