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Category: bioengineering

Generative AI Designs Synthetic Gene Editing Proteins Better than Nature

Researchers from Integra Therapeutics, in partnership with the Pompeu Fabra University (UPF) and the Centre for Genomic Regulation (CRG), Spain, have used generative AI to design synthetic proteins that outperform naturally occurring proteins used for editing the human genome. Their use of generative AI focused on PiggyBac transposases, naturally occurring enzymes that have long been used for gene delivery and genetic engineering, and uncovered more than 13,000 previously unidentified PiggyBac sequences. The research, published in Nature Biotechnology, has the potential to improve current gene editing tools for the creation of CAR T and gene therapies.

“Our work expands the phylogenetic tree of PiggyBac transposons by two orders of magnitude, unveiling a previously unexplored diversity within this family of mobile genetic elements,” the researchers wrote.

For their work, the researchers first conducted extensive computational bioprospecting, screening more than 31,000 eukaryotic genomes to uncover the 13,000 new sequences. From this number, the team was able to validate 10 active transposases, two of which showed similar activity to PiggyBac transposases currently used in both research and clinical settings.

Scientists reverse Alzheimer’s in mice using nanoparticles

A research team co-led by the Institute for Bioengineering of Catalonia (IBEC) and West China Hospital Sichuan University (WCHSU), working with partners in the UK, has demonstrated a nanotechnology strategy that reverses Alzheimer’s disease in mice.

Unlike traditional nanomedicine, which relies on nanoparticles as carriers for therapeutic molecules, this approach employs nanoparticles that are bioactive in their own right: “supramolecular drugs.” The work has been published in Signal Transduction and Targeted Therapy.

Instead of targeting neurons directly, the therapy restores the proper function of the blood-brain barrier (BBB), the vascular gatekeeper that regulates the brain’s environment. By repairing this critical interface, the researchers achieved a reversal of Alzheimer’s pathology in animal models.

Fat particles could be key to treating metabolic brain disorders

Evidence challenging the long-held assumption that neuronal function in the brain is solely powered by sugars has given researchers new hope of treating debilitating brain disorders. A University of Queensland study led by Dr. Merja Joensuu and published in Nature Metabolism showed that neurons also use fats for fuel as they fire off the signals for human thought and movement.

“For decades, it was widely accepted that relied exclusively on glucose to fuel their functions in the brain,” Dr. Joensuu said. “But our research shows fats are undoubtedly a crucial part of the neuron’s in the brain and could be a key to repairing and restoring function when it breaks down.”

Dr. Joensuu from the Australian Institute for Bioengineering and Nanotechnology along with lab members Ph.D. candidate Nyakuoy Yak and Dr. Saber Abd Elkader from UQ’s Queensland Brain Institute set out to examine the relationship of a particular gene (DDHD2) to hereditary spastic paraplegia 54 (HSP54).

Researchers eye bio-hybrid robots with engineered and biological parts for self-healing, energy efficiency

Officials of the U.S. Defense Advanced Research Projects Agency (DARPA) in Arlington, Va., issued an advanced research concepts opportunity earlier this month (DARPA-EA-25–02-02) for the Hybridizing Biology and Robotics through Integration for Deployable Systems (HyBRIDS) program.

Bio-hybrid robotics

Bio-hybrid robotics combines living organisms and synthetic materials to create biorobots that compared to traditional robots can offer adaptability, self-healing, and energy efficiency.

New Cas9 Enzymes Improve the Accuracy of CRISPR Prime Editing

The CRISPR gene editing system holds tremendous promise. It has already revolutionized biomedical research by making gene editing a straightforward process. It involves using a guide RNA molecule that has a unique sequence, which matches with a target location in genomic DNA. This guide RNA brings an enzyme called Cas9 to that genetic location, where Cas9 makes a cut in the DNA. Scientists have been modifying and improving on the CRISPR technique since it was created. Many of those improvements are related to the Cas9 enzyme, and ensuring that it makes the proper cut in the correct place.

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.

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