Lifeboat Foundation

CRISPR gene editing already promises to fight diseases that were once thought unassailable, but techniques so far have required injecting the tools directly into affected cells. That’s not very practical for some conditions. However, there’s just been a breakthrough. NPR reports that researchers have published results showing that you can inject CRISPR-Cas9 into the bloodstream to make edits, opening the door to the use of gene editing for treating many common diseases.

The experimental treatment tackled a rare genetic disease, transthyretin amyloidosis. Scientists injected volunteers with CRISPR-loaded nanoparticles that were absorbed by the patients’ livers, editing a gene in the organ to disable production of a harmful protein. Levels of that protein plunged within weeks of the injection, saving patients from an illness that can rapidly destroy nerves and other tissues in their bodies.

The test involved just six people, and the research team still has to conduct long-term studies to check for possible negative effects. If this method proves viable on a large scale, though, it could be used to treat illnesses where existing CRISPR techniques aren’t practical, ranging from Alzheimer’s to heart disease.

Now, in a medical first, researchers have injected a CRISPR drug into the blood of people born with a disease that causes fatal nerve and heart disease and shown that in three of them it nearly shut off production of toxic protein by their livers.

Novel treatment using messenger RNA sharply cuts production of mutant liver protein, although it’s too early to show patients with rare condition benefit.

👏😄We are rapidly approaching — from multiple directions of attack (pharmaceutical, nanotechnology, gene manipulation, etc) — the end of all forms of cancer, inherited diseases, even aging itself. It’s a great time to be alive IF you can live long enough to live forever(ish)! Which makes EVERY death that occurs in the meantime to be all the more of a punch to the gut and slap to the face. PARTICULARLY the 600 000 + people here in the US alone! It’s also another reason t… See More.

If the gene-editing tool CRISPR/Cas9 continues to show such promise it will herald a new era for the treatment of many genetic diseases.

Scientists successfully treated a rare disease with the experimental gene-editing technique. It could open the door to new ways of treating more common disorders in the future.

Move over, gene-editing proteins—there’s a smaller, cheaper, more specific genetic engineering tool on the block: DNAzymes—small DNA molecules that can function like protein enzymes.

Researchers at the University of Illinois Urbana-Champaign have developed a technique that, for the first time, allows DNAzymes to target and cut double-stranded DNA, overcoming a significant limitation of the technology. DNAzymes have been used in biosensing, DNA computing and many other applications. However, when it comes to genetic engineering applications such as gene editing or gene therapy, they have faced a challenge: DNAzymes have only been able to target sites on single-stranded DNA, while the DNA coding for genes in cells is double-stranded. The researchers published their new technique in the Journal of the American Chemical Society.

“DNAzymes have many advantages, including higher stability, smaller size and lower cost than protein enzymes. These advantages perfectly fit the requirement for genetic engineering tools,” said study leader Yi Lu, a professor of chemistry at Illinois. “No DNAzymes could alter double-stranded DNA until this work. By making that happen, we open the door for DNAzymes to enter the entire world of genetic engineering.”

To understand how the clones can create millions of copies of themselves and yet remain functional, Oldroyd and his team compared the genomes of Cape honeybee workers with those of their queen and her offspring.

After forcing the Cape queen to reproduce asexually by fitting her with surgical tape that prevented her from mating, the team examined certain DNA sequences of both the Cape queen and the 25 larvae she produced. Then, they did the same for four Cape honeybee workers and their 63 larvae.

The team discovered that the asexually reproduced offspring of the queen had levels of recombination (DNA mixing) 100 times greater than the genetically identical cloned offspring of the workers — a finding that suggests the Cape worker bees have evolved a mutation that prevents recombination. Without the risk of a one-third loss of genetic material caused by the asexual reshuffling process, the workers are free to continually create perfect copies of themselves.

Genome-embedded ribonucleotides arrest replicative DNA polymerases (Pols) and cause DNA breaks. Whether mammalian DNA repair Pols efficiently use template ribonucleotides and promote RNA-templated DNA repair synthesis remains unknown. We find that human Polθ reverse transcribes RNA, similar to retroviral reverse transcriptases (RTs). Polθ exhibits a significantly higher velocity and fidelity of deoxyribonucleotide incorporation on RNA versus DNA. The 3.2-Å crystal structure of Polθ on a DNA/RNA primer-template with bound deoxyribonucleotide reveals that the enzyme undergoes a major structural transformation within the thumb subdomain to accommodate A-form DNA/RNA and forms multiple hydrogen bonds with template ribose 2′-hydroxyl groups like retroviral RTs. Last, we find that Polθ promotes RNA-templated DNA repair in mammalian cells. These findings suggest that Polθ was selected to accommodate template ribonucleotides during DNA repair.

Polymerase θ (Polθ) is a unique DNA polymerase-helicase fusion protein in higher eukaryotes whose A-family polymerase domain evolved from Pol I enzymes (Fig. 1A) (1, 2). However, contrary to most Pol I enzymes, Polθ is highly error-prone and promiscuous (3–6), performs translesion synthesis (TLS) opposite DNA lesions (3, 7, 8), and facilitates microhomology-mediated end-joining (MMEJ) of double-strand breaks (DSBs) by extending partially base-paired 3′ single-stranded DNA (ssDNA) overhangs at DSB repair junctions (5, 9–12). Polθ is not expressed in most tissues but is highly expressed in many cancer cells, which corresponds to a poor clinical outcome (13, 14). Furthermore, Polθ confers resistance to genotoxic cancer therapies and promotes the survival of cells deficient in DNA damage response pathways (11, 13–16). Thus, Polθ represents a promising cancer drug target.

Intriguingly, Polθ has an inactive proofreading domain due to acquired mutations (Fig. 1A) (2). Inactivating the 3′-5′ proofreading function of closely related A-family bacterial Pol I Klenow fragment (KF) enables this polymerase to reverse transcribe RNA like retroviral reverse transcriptases (RTs), which lack proofreading activity (fig. S1A) (17, 18). Because Polθ is highly error-prone and promiscuous and contains an inactive proofreading domain, we hypothesized that it has RNA-dependent DNA synthesis activity. Given that ribonucleotides are the most frequently occurring nucleotide lesion in genomic DNA that arrest replicative Pols and cause DNA breaks (19, 20), we also envisaged that Polθ would tolerate template ribonucleotides during its DNA repair activities and thus promote RNA-templated DNA repair synthesis (RNA-DNA repair). Although RNA-DNA repair mechanisms have been demonstrated in genetically engineered yeast cells (21, 22), they remain obscure in mammalian cells.

STANFORD, Calif. — A groundbreaking “superhero” vaccine inspired by the DNA code of Olympic athletes could help transform society over the next decade, a top genetic scientist claims.

The vaccine would provide lifelong protection against three of the top ten leading causes of death, according to Euan Ashley, professor of medicine and genetics at Stanford University. The so-called “superhero” jab could offer simultaneous, long-term protection against heart disease, stroke, Alzheimer’s disease, and liver disease, thanks to advances in genetic engineering.

This breakthrough treatment would deliver the blueprint of “ideal” cells from men and women whose genes are more disease-resistant than those of the average person, together with an “instruction manual” to help the body “repair, tweak and improve” its own versions. A single dose could lead to a “body-wide genetic upgrade” that would cut the risk of premature death in some adults by as much as 50 percent.

“At first, we had a hard time believing the results. Many of these genes are classical hallmarks of aging and yet our results suggested that their activity is more a function of the presence of bacteria rather than the aging process,” said Dr. Shukla.

Notably, this included genes that control stress and immunity. The researchers tested the impact that the antibiotics had on these genes by starving some flies or infecting others with harmful bacteria and found no clear trend. At some ages, the antibiotics helped flies survive starvation or infection longer than normal whereas at other ages the drugs either had no effect or reduced the chances of survival.

NIH scientists discover that bacteria may drive activity of many hallmark aging genes in flies.

Continue reading “Study suggests scientists may need to rethink which genes control aging” »