Lifeboat Foundation: Safeguarding Humanity
Toggle light / dark theme

Blog

Category: bioengineering

Mapping RNA-protein ‘chats’ could uncover new treatments for cancer and brain disease

Bioengineers at the University of California San Diego have developed a powerful new technology that can map the entire network of RNA-protein interactions inside human cells—an achievement that could offer new strategies for treating diseases ranging from cancer to Alzheimer’s.

RNA-protein interactions regulate many essential processes in cells, from turning genes on and off to responding to stress. But until now, scientists could only capture small subsets of these interactions, leaving much of the cellular “conversation” hidden.

“This technology is like a wiring map of the cell’s conversations,” said Sheng Zhong, professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering, who led the study published in Nature Biotechnology.

Heat-rechargeable design powers nanoscale molecular machines

Though it might seem like science fiction, scientists are working to build nanoscale molecular machines that can be designed for myriad applications, such as “smart” medicines and materials. But like all machines, these tiny devices need a source of power, the way electronic appliances use electricity or living cells use ATP (adenosine triphosphate, the universal biological energy source).

Researchers in the laboratory of Lulu Qian, Caltech professor of bioengineering, are developing nanoscale machines made out of synthetic DNA, taking advantage of DNA’s unique chemical bonding properties to build circuits that can process signals much like miniature computers. Operating at billionth-of-a-meter scales, these molecular machines can be designed to form DNA robots that sort cargos or to function like a neural network that can learn to recognize handwritten numerical digits.

One major challenge, however, has remained: how to design and power them for multiple uses.

Human genome rearrangement with programmable bridge recombinases

Bridge recombinases were discovered from parasitic mobile genetic elements that hijack bacterial genomes for their own survival. Presented last year in the journal Nature, the same team found these elements encode both a new class of structured guide RNA, which they named a “bridge RNA”, and a recombinase enzyme that rearranges DNA. The researchers repurposed this natural system by reprogramming the bridge RNA to target new DNA sequences, creating the foundation for a new type of precise gene editing tool they called bridge recombinases.

Starting with 72 different natural bridge recombinase systems isolated from bacteria, the team found that about 25% showed some activity in human cells, but most were barely detectable. Only one system, called ISCro4, showed enough measurable activity to enable further optimization. They then systematically improved both the protein and its RNA guide components, testing thousands of variations until they achieved 20% efficiency for DNA insertions and 82% specificity for hitting intended targets in the human genome.

While CRISPR uses a single guide RNA to target one DNA location, bridge RNAs are unique because they can simultaneously recognize two different DNA targets through distinct binding loops. This dual recognition enables the system to perform coordinated rearrangements such as bringing together distant chromosomal regions to excise genetic material or flipping existing sequences in reverse orientation. The system acts as molecular scaffolding that holds two DNA sites together while the recombinase enzyme performs the rearrangement reaction.

As a proof-of-concept, the researchers created artificial DNA constructs containing the same toxic repeat sequences that cause progressive neuromuscular decline in Friedreich’s ataxia patients. While healthy individuals carry fewer than 10 sequential copies of a three-letter DNA sequence, people with the disorder can harbor up to 1,700 copies, which interferes with normal gene function. The engineered ISCro4 successfully removed these repeats from the artificial constructs, in some cases eliminating over 80% of the expanded sequences.

The team also demonstrated that bridge recombinases could replicate existing therapeutic approaches by successfully removing the BCL11A enhancer, the same target disrupted in an FDA-approved sickle cell anemia treatment. And because bridge recombinases can move massive amounts of DNA, the technology could also help model the large-scale genomic rearrangements associated with cancers.

For decades, gene-editing science has been limited to making small, precise edits to human DNA, akin to correcting typos in the genetic code. The researchers are changing that paradigm with a universal gene editing system that allows for cutting and pasting of entire genomic paragraphs, rearranging whole chapters, and even restructuring entire passages of the genomic manuscript.

Continue reading “Human genome rearrangement with programmable bridge recombinases” | >

AggreBots: Tiny living robots made from lung cells could one day deliver medicine inside the body

A brand-new engineering approach to generate “designer” biological robots using human lung cells is underway in Carnegie Mellon University’s Ren lab. Referred to as AggreBots, these microscale living robots may one day be able to traverse through the body’s complex environments to deliver desired therapeutic or mechanical interventions, once greater control is achieved over their motility patterns. In new research published in Science Advances, the group provides a novel tissue engineering platform capable of achieving customizable motility in AggreBots by actively controlling their structural parameters.

Biobots are microscopic, man-made biological machines capable of autonomous movement and programmability to perform specific tasks or behaviors. Previously, enabling biobots’ motility has been centered around using , which allow them to move by contracting and relaxing like real muscles.

A novel, alternative mechanism of actuation can be found by using cilia, the nanoscopic, hair-like, organic propellers that continuously move fluids in the body (like in the lungs) and help some aquatic creatures, like Paramecium or comb jellies, swim. However, a reliable way to control the exact shape and structure of a cilia-powered biobot (CiliaBot, for short), and thereby its motility outcome, has proven difficult to come by.

Bridge recombinases, optimized for human cells, enable massive programmable DNA rearrangements

For decades, gene-editing science has been limited to making small, precise edits to human DNA, akin to correcting typos in the genetic code. Arc Institute researchers are changing that paradigm with a universal gene editing system that allows for cutting and pasting of entire genomic paragraphs, rearranging whole chapters, and even restructuring entire passages of the genomic manuscript.

Enhanced CAR T cells emerge from genetic screening

CAR T cells are patient-derived, genetically engineered immune cells. They are “living drugs” and constitute a milestone in modern medicine. Equipping T cells, a key cell type of the immune system, with a “chimeric antigen receptor” (CAR) enables them to specifically recognize and attack cancer cells.

CAR T cell therapy has demonstrated its potential by curing patients with otherwise untreatable blood cancers. But it still fails for most patients, often due to T cell intrinsic dysfunction. To address their current limitations and to make CAR T cells intrinsically stronger, scientists at the CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences and the Medical University of Vienna have developed a new method for systematic discovery of genetic boosters of CAR T cell function.

The new study, published in Nature, introduces CELLFIE, a CAR T cell engineering and high-content CRISPR screening platform, enabling researchers to systematically modify CAR T cells and evaluate their therapeutic potential.

Bilu Huang — CSO, Fuzhuang Therapeutics — Conquering Aging Via TRCS

Conquering aging via TRCS — the telomere DNA AND ribosomal DNA co-regulation model for cell senescence — bilu huang — CSO, fuzhuang therapeutics.

Bilu Huang (https://biluhuang.com/) is a visionary scientist dedicated to finding solutions to some of the most pressing challenges facing humanity. His interdisciplinary work spans multiple fields, including biological aging, dinosaur extinction theories, geoengineering for carbon removal, and controlled nuclear fusion technology.

Born in Sanming City, Fujian Province, Huang is an independent researcher whose knowledge is entirely self-taught. Driven by curiosity and a relentless pursuit of scientific exploration, he has achieved numerous research results through his dedication and passion for science.

As a talented theoretical gerontologist, he proposed the Telomere DNA and ribosomal DNA co-regulation model for cell senescence (TRCS) and he is now using this latest theory to develop biotechnology to rejuvenate cells which will be used to completely cure various age-related degenerative diseases and greatly extend human life at Fuzhuang Therapeutics (https://lab.fuzhuangtx.com/en/).

#Aging #Longevity #BiluHuang #FuzhuangTherapeutics #TelomereDNAAndRibosomalDNACoRegulationModelForCell #Senescence #TRCS #DinosaurExtinctionResearch #CarbonRemovalTechnology #ControlledNuclearFusion #TelomereDNA #RibosomalDNA #CellularAging #GeneticProgram #Telomere #P53

Continue reading “Bilu Huang — CSO, Fuzhuang Therapeutics — Conquering Aging Via TRCS” | >

Engineered gut bacteria improve survival outcomes in colorectal cancer tumors

In a new study that combines synthetic biology with cancer immunotherapy, researchers from the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) and Central South University in China have developed an engineered strain of gut-homing bacteria that stimulates potent antitumor immune responses against colorectal cancer (CRC).

Antitumor immune responses refer to the actions taken by the body’s immune system to recognize, attack, and destroy . It operates like the body’s internal surveillance system, spotting rogue cells (like ) and activating its defense forces to eliminate them.

Harnessing the immune system to fight cancer offers a powerful and precise approach to disease control. Unlike traditional treatments such as chemotherapy or radiation, which can harm healthy cells, immune responses can selectively target and destroy cancer cells with high specificity.

/* */