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Category: biotech/medical – Page 10

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.

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.

World’s First “Perovskite Camera” Can See Inside the Human Body

A new detector aims to reduce costs while improving the quality of nuclear medicine. Physicians use nuclear medicine techniques such as SPECT scans to observe how the heart pumps, follow patterns of blood flow, and identify diseases that are otherwise hidden deep within the body. Current scanners

Stanford Scientists Rethink How We Learn To Move in the World

Knight Initiative researchers are investigating the detailed processes behind how the brain learns to control movement. Their discoveries may eventually lead to improved therapies for Parkinson’s disease. Every motor skill you acquire, from simple actions like walking to precise tasks such as wat

Scientists Train AI to Forecast Over 1,000 Diseases, Years in Advance

Scientists said Wednesday that they had created an AI model able to predict medical diagnoses years in advance, building on the same technology behind consumer chatbots like ChatGPT.

Based on a patient’s case history, the Delphi-2M AI “predicts the rates of more than 1,000 diseases” years into the future, the team from British, Danish, German and Swiss institutions wrote in a paper published in the journal Nature.

Researchers trained the model on data from Britain’s UK Biobank – a large-scale biomedical research database with details on about half a million participants.

Rapamycin linked to DNA damage resilience in aging human immune cells

University of Oxford-led research finds low-dose rapamycin functions as a genomic protector in aging human immune cells, lowering DNA damage.

The mechanistic target of rapamycin (mTOR) is a central signaling pathway that regulates and coordinates cell growth, metabolism, and survival in response to environmental cues. It helps cells integrate signals from growth factors, nutrients, and stress to control whether they are in an anabolic (building up) or catabolic (breaking down) state.

Aging immune systems accumulate DNA damage linked to immunosenescence. Rapamycin is a drug that inhibits the mTOR pathway. Originally developed for organ transplantation to prevent immune rejection, previous research has found that, at non-immunosuppressive doses, rapamycin can mitigate cellular senescence.

Is Chronic Kidney Disease Due to Cadmium Exposure Inevitable and Can It Be Reversed?

Cadmium (Cd) is a metal with no nutritional value or physiological role. However, it is found in the body of most people because it is a contaminant of nearly all food types and is readily absorbed. The body burden of Cd is determined principally by its intestinal absorption rate as there is no mechanism for its elimination. Most acquired Cd accumulates within the kidney tubular cells, where its levels increase through to the age of 50 years but decline thereafter due to its release into the urine as the injured tubular cells die. This is associated with progressive kidney disease, which is signified by a sustained decline in the estimated glomerular filtration rate (eGFR) and albuminuria. Generally, reductions in eGFR after Cd exposure are irreversible, and are likely to decline further towards kidney failure if exposure persists.

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