Developing nonviral gene delivery system in Primate

new option in human disease research

Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University

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Genetic engineering in non-human primates has long been limited by the need for virus-based gene delivery methods. Recently, researchers in Japan successfully used a nonviral system to introduce a transgene—that is, a gene that has been artificially inserted into an organism—into cynomolgus monkeys, which is a species of primate closely related to humans.

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Credit: ASHBi/Kyoto University

Genetic engineering in non-human primates has long been limited by the need for virus-based gene delivery methods. Recently, researchers in Japan successfully used a nonviral system to introduce a transgene—that is, a gene that has been artificially inserted into an organism—into cynomolgus monkeys, which is a species of primate closely related to humans.

 

Small animal models such as mice do not fully replicate the complexity of human diseases, particularly in areas like infectious disease and neuropsychiatric disorders. This limitation has made non-human primates an essential model for biomedical research. However, genetic modification of these primates has been challenging. For example, conventional virus-based methods require specialized containment facilities and are limited in terms of the size of transgenes that the viruses can carry. Also, these methods do not allow for precise selection of modified embryos before implantation.

 

To overcome these challenges, the research team sought an alternative to using viruses to carry transgenes, instead opting for a nonviral piggyBac transposon system. Transposons, which are sequences of DNA that can change positions within a genome, are valuable tools for gene transfer in genetic engineering as they can stably integrate genetic material into the host’s DNA. The piggyBac transposon system offers several advantages over traditional virus-based approaches, including greater flexibility in terms of the size of transgenes that can be carried and the ability to confirm successful modifications at the early embryo stage.  This allows for more efficient embryo screening before implantation, increasing the likelihood of producing genetically modified animals that carry the desired traits.

 

Using this approach, the team successfully generated transgenic cynomolgus monkeys, marking a major advancement in genetic engineering. In the resulting cynomolgus monkeys, there was widespread expression of fluorescent reporter genes (that is, the production of fluorescent reporter proteins based the genetic information). Red fluorescent protein was localized to cell membranes, and green fluorescent protein was localized to cell nuclei. Expression was confirmed across all tissues examined, including germ cells, demonstrating that the transgene was stably introduced. These findings suggest that the piggyBac transposon system has significant potential for creating genetically modified primates, which could be used to study human disease in ways that traditional rodent models cannot replicate.

 

While the transgene integration pattern was consistent across different tissues, expression levels varied. This variability underscores the need in future applications to carefully select promoters—the regulatory regions of DNA that turn on and off specific genes—based on the target tissue. For example, genes such as OCT3/4 and DDX4 play important roles in germ cell lineage differentiation, while SYN1 and THY1 are involved in Neuronal lineage differentiation. By selecting appropriate promoters for specific tissues, researchers can fine-tune gene expression to achieve the desired effects, an essential step in advancing genetic models for disease research.

“Our research represents a milestone in the field of genetic engineering,” explains Dr. Tomoyuki Tsukiyama who led this project. “Our method provides a practical and efficient way to introduce transgenes into non-human primates, which we hope will unlock new insights into complex human diseases.”

 

Looking ahead, the team plans to expand the applications of this system to include multiplex gene expression and precise transgene control, thereby allowing for more sophisticated genetic models. In addition, the researchers are exploring the potential for integrating epigenetic data about how genes are turned on and off into their work in order to better understand how gene expression is regulated at the molecular level. By refining these techniques, the researchers aim to explore disease mechanisms that remain inaccessible in rodent models and ultimately improve our understanding of complex health conditions in humans.

 

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About Institute for the Advanced Study of Human Biology (ASHBi), Kyoto University

What key biological traits make us ‘human’, and how can knowing these lead us to better cures for disease? ASHBi investigates the core concepts of human biology with a particular focus on genome regulation and disease modeling, creating a foundation of knowledge for developing innovative and unique human-centric therapies.

About the World Premier International Research Center Initiative (WPI)

The WPI program was launched in 2007 by Japan's Ministry of Education, Culture, Sports, Science and Technology (MEXT) to foster globally visible research centers boasting the highest standards and outstanding research environments. Numbering more than a dozen and operating at institutions throughout the country, these centers are given a high degree of autonomy, allowing them to engage in innovative modes of management and research. The program is administered by the Japan Society for the Promotion of Science (JSPS).  

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Journal

Nature Communications

DOI

10.1038/s41467-025-57365-w 

Method of Research

Experimental study

Subject of Research

Animals

Article Title

Non-viral generation of transgenic non-human primates via the piggyBac transposon system.

Article Publication Date

24-Mar-2025

 

KAIST develops eco-friendly, nylon-like plastic using microorganisms​

The Korea Advanced Institute of Science and Technology (KAIST)

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Photo 1. (From left) Professor Sang Yup Lee, Dr. Tong Un Chae, Dr. So Young Choi, and Ph.D. candidate Da-Hee Ahn of the Department of Chemical and Biomolecular Engineering

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Credit: KAIST Metabolic and Biomolecular Engineering National Research Laboratory

Poly(ester amide) amide is a next-generation material that combines the advantages of PET (polyester) and nylon (polyamide), two widely used plastics. However, it could only be produced from fossil fuels, which posed environmental concerns. Using microorganisms, KAIST researchers have successfully developed a new bio-based plastic to replace conventional plastic.

 

< Photo 1. (From left) Professor Sang Yup Lee, Dr. Tong Un Chae, Dr. So Young Choi, and Ph.D. candidate Da-Hee Ahn of the Department of Chemical and Biomolecular Engineering >

 

KAIST (represented by President Kwang Hyung Lee) announced on the 20th of March that a research team led by Distinguished Professor Sang Yup Lee from the Department of Chemical and Biomolecular Engineering has developed microbial strains through systems metabolic engineering to produce various eco-friendly, bio-based poly(ester amide)s. The team collaborated with researchers from the Korea Research Institute of Chemical Technology (KRICT, President Young-Kook Lee) to analyze and confirm the properties of the resulting plastic.

Professor Sang Yup Lee’s research team designed new metabolic pathways that do not naturally exist in microorganisms, and developed a platform microbial strain capable of producing nine different types of poly(ester amide)s, including poly(3-hydroxybutyrate-ran-3-aminopropionate) and poly(3-hydroxybutyrate-ran-4-aminobutyrate).

Using glucose derived from abundant biomass sources such as waste wood and weeds, the team successfully produced poly(ester amide)s in an eco-friendly manner. The researchers also confirmed the potential for industrial-scale production by demonstrating high production efficiency (54.57 g/L) using fed-batch fermentation of the engineered strain.

In collaboration with researchers Haemin Jeong and Jihoon Shin from KRICT, the KAIST team analyzed the properties of the bio-based plastic and found that it exhibited characteristics similar to high-density polyethylene (HDPE). This means the new plastic is not only eco-friendly but also strong and durable enough to replace conventional plastics.

 

< Figure 1. New-to-nature metabolic pathways for the production of poly(ester amide)s (PEAs). >

 

The engineered strains and strategies developed in this study are expected to be useful not only for producing various poly(ester amide)s but also for constructing metabolic pathways for the biosynthesis of other types of polymers.

Professor Sang Yup Lee stated, “This study is the first to demonstrate the possibility of producing poly(ester amide)s (plastics) through a renewable bio-based chemical process rather than relying on the petroleum-based chemical industry. We plan to further enhance the production yield and efficiency through continued research.”

The study was published online on March 17 in the international journal Nature Chemical Biology.

·Title: Biosynthesis of poly(ester amide)s in engineered Escherichia coli

·DOI: 10.1038/s41589-025-01842-2

·Authors: A total of seven authors including Tong Un Chae (KAIST, first author), So Young Choi (KAIST, second author), Da-Hee Ahn (KAIST, third author), Woo Dae Jang (KAIST, fourth author), Haemin Jeong (KRICT, fifth author), Jihoon Shin (KRICT, sixth author), and Sang Yup Lee (KAIST, corresponding author).

This research was supported by the Ministry of Science and ICT (MSIT) under the Eco-Friendly Chemical Technology Development Project as part of the "Next-Generation Biorefinery Technology Development to Lead the Bio-Chemical Industry" initiative (project led by Distinguished Professor Sang Yup Lee at KAIST).

Figure 1. New-to-nature metabolic pathways for the production of poly(ester amide)s (PEAs).

Credit

KAIST Metabolic and Biomolecular Engineering National Research Laboratory

Usage Restricti

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Journal

Nature Chemical Biology

DOI

10.1038/s41589-025-01842-2 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Biosynthesis of poly(ester amide)s in engineered Escherichia coli

Article Publication Date

25-Mar-2025

COI Statement

Tong Un Chae, So Young Choi, Da-Hee Ahn and Sang Yup Lee declare competing financial interests because the strains, PEAs and strategies described in this paper are of commercial interest and are covered by but not limited to a pending patent (Korean Patent Application No. 10-2025-0009527). This patent covers the methods for producing PEAs using engineered strains in this study. The patent was filed by the Korea Advanced Institute of Science and Technology and Sang Yup Lee, Tong Un Chae, So Young Choi and Da-Hee Ahn are listed as inventors. The other authors declare no competing interests.

 

Hydrophilic coating makes for unflappable golf balls

American Chemical Society

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This specialized golf ball looks and feels smooth, but a close examination under a standard light microscope reveals tiny crystals of absorbent silica and polymers dotting the surface.

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Credit: Thomas J. Kennedy III

SAN DIEGO, March 25, 2025 — The upcoming U.S. Open has professional golfers and spectators looking forward to getting on the green. But the grass’ condition, regardless of a player’s skill, can drastically skew the chances of a winning putt. Now, scientists can slow the roll of a golf ball on a lightning-fast, dry course and speed it up on a sluggish, wet course thanks to a coating that soaks up water molecules without interfering with the ball’s aerodynamics.

Thomas J. Kennedy III, owner of Chemical Innovative Solutions Inc., will present his results at the spring meeting of the American Chemical Society (ACS). ACS Spring 2025 is being held March 23-27; it features about 12,000 presentations on a range of science topics.

“I was thinking about a way to help golfers and the game of golf overall by improving the putting process so that having a good round was not a matter of chance but a matter of skill,” says Kennedy, who has been in the golf ball business for decades and has loved the game since he was a child.

Previously, Kennedy, a polymer chemist and inventor, developed state-of-the-art golf balls that optimized long-distance performance in the air. But with his new project, he focuses on the interaction between the ball and the grass. “Golf in many ways is a surface interaction game,” he says, “with the putter imparting spin rates on the ball, as well as the grass affecting how fast or slow the ball rolls toward the hole.”

A dry putting green — like the ones Oakmont Country Club, home of this year’s U.S. Open, is known for — can be lightning-fast, but wet grass creates an almost sticky runway. So, Kennedy created a hydrophilic (water-loving) coating that modifies the surface-to-surface interaction between the ball and the green. The coating increases the surface energy of the ball — the opposite of what hot wax does to a car hood. So, instead of beading up, the water absorbs or sheets off the surface. On dry grass, the coating draws up water to slow down the ball. On wet grass, the coating helps release the green’s grip on the ball. 

Kennedy says the new coating wouldn’t be considered cheating, rather it boosts a player’s already-honed skills.

“The United States Golf Association (USGA) has set standards for golf balls: There’s a size limit, a weight limit, a symmetry constraint and there’s even a standard for overall distance traveled,” he shares. “But within that box, there’s a lot of latitude to do different things that change the playability of golf balls while staying within the confines of the USGA and the Royal and Ancient Golf Club of St Andrews rules.”

The new coating contains absorbent materials, such as amorphous silica, molecular sieves, clay and fast-exfoliating polyacrylic acid polymer. Kennedy tuned the molecular sieves to only absorb water-sized molecules. He also varied the ratios of absorbent compounds to create a coating that provides the right amount of traction but doesn’t impact the ball’s flight once it’s popped into the air. 

To test the coating’s effect on fast and slow greens, Kennedy used a Stimpmeter — a V-shaped metal rod that applies a known velocity to the ball. Kennedy uses the rod as a ramp for rolling a coated or uncoated ball so that the distance it travels on a dry or wet green can be measured and compared. His experiments revealed that the coated golf balls had a more consistent speed on both dry and wet simulated greens compared to the uncoated ones.

For the average golfer, these results could mean finishing 18 holes on par. For the professional golfer, they could mean fewer strokes and a much bigger paycheck.

In addition to a better golf game, Kennedy says the coating could be applied to solar panels to improve their performance. “It may sound counterintuitive,” he explains, “but the hydrophilic nature of the coating keeps solar panels cleaner by allowing water to soak the surface and wash away sun-blocking dust and debris.”

Kennedy has provisional patents for the use of the hydrophilic coating on golf balls and solar panels. In a few months, he says these innovative golf balls may make an appearance on a golf course near you.

“The game of golf has been around since the 15th century. However, there’s always a new way to look at something as technology evolves,” says Kennedy. “Innovation and invention know no bounds!”

The research was funded by Chemical Innovative Solutions Inc.

Visit the ACS Spring 2025 program to learn more about this presentation, “Hydrophilic modified coatings for golf balls” and other science presentations. 

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Title
Hydrophilic modified coatings for golf balls

Abstract
The game of golf, for the most part, is played in an outdoor environment where weather conditions can play a significant part in the performance of the players and the performance of the player's equipment. Very wet weather causes the fairways, rough, and putting greens to become soft and sometimes soggy. These conditions will consequently slow the roll of the golf ball. Conversely, very warm and dry weather causes the fairways and especially putting greens to allow for much greater roll of the golf ball, know in the golf vernacular as being "fast. Unfortunately, particularly in the case of very fast putting greens, the game of golf is altered so as to be in some cases, almost unplayable.

One remedy to this issue of fast greens is to produce a golf ball that has similar traction on the putting green no mater what the putting surface is like; fast or slow. One way to achieve this is to modify the coating on the golf ball. The modification of the hydrophilic nature of the exterior coatings on golf balls allows for the golf ball to have a slower roll on even very fast greens. However, the modification of the exterior coating must not be such that the modification affects the aerodynamics of the golf ball in flight. Thus the hydrophilic change to the golf ball coating must be transient or minimal but enough to affect the roll of the golf ball on a grass surface.

Through a combination of absorbent materials such as amorphous silica, molecular sieves and clay along with new super absorbing materials such as fast exfoliating polyacrylic acid polymer with initiators such as azobisisobutyronitrile and benzoyl peroxide. By varying the initiator and the absorbent material, the hydrophilic nature of the golf ball coating may be increased or decreased.
These various golf ball coatings are shown to modify the roll of the golf ball on the green through Stimpmeter testing on fast greens (greater than 10).

 

Canada slowest in reporting bird flu at 618 days – but COVID shows we can do better

University of British Columbia

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The global average for countries to report genetic information about bird flu, crucial to tracking and preventing a human pandemic, was seven months, and Canada came in last, a new study has found.

Authors of the non-peer reviewed commentary published today in Nature Biotechnology say the work highlights the urgent need for Canada and other countries to speed up the pipeline from sampling an infected creature, analysis of the genetic information, and submission to a global scientific database.

Dr. Sarah Otto (SO), professor in the department of zoology, and Sean Edgerton (SE) (he/him), zoology doctoral student, discuss why getting this information quickly is crucial, and how Canada has pulled its socks up once before.

Why do we need this data?

SO: We need to track the evolution of viruses if we are to have any hope of preventing another pandemic. The particular ‘flu strain we’re worried about, H5N1, has wreaked havoc on the dairy and poultry industry in several countries and spread to hundreds of species of birds and mammals, but so far, the virus has not evolved the features needed to spread efficiently among humans. With real-time genetic data being submitted from around the world, we can keep an eye on these features and, if we see this evolution, raise the alarm.

We did this with the COVID variants. By tracking the virus’ evolution through genetic data, we were able to provide advanced warnings about the spread of variants, allowing public health responses such as increasing hospital capacity and quickly offering vaccines to those most at risk. Together, we saved lives.

What did you find?

SE: We looked at close to 19,000 H5N1 samples from January 2021 to December 2024 on a global database, the Global Initiative for Sharing All Influenza Data (GISAID). We measured the time taken from when a sample of the virus was collected from an animal or human through analysis of the genetic data to submission to this database, where it’s then available for other scientists to study. We then calculated the average per country submitting at least 50 sequences. We found the global average was about 228 days. Canada was the slowest at 618 days on average. The fastest countries were the Czech Republic and the Netherlands at only 25 days on average.

It was a bit shocking how long it took especially for a virus with pandemic potential like H5N1.

Why are the delays this long?

SO: We’re not sure, but the delays could be due to the number of different institutions involved in the entire collection, analysis, and submission process. In addition, there is little targeted funding to monitor H5N1 in Canadian wildlife, so most efforts to monitor the spread of this highly pathogenic flu virus are piggy-backing on other studies.

What can we do?

SO: I know we can get better. Canada improved submission times dramatically for SARS-CoV-2, dropping data delays from about 88 days to 16. Canada is now one of the strongest and most efficient countries informing the world about changes to the virus that causes COVID-19. We can do the same with H5N1.

We are also concerned about recent restrictions on gathering and sharing information in the United States, with widespread firing of government scientists and restrictions on data sharing. Wildlife don’t care about borders, so Canada needs to step up to the plate and monitor what’s happening in North America to help alert ourselves and other countries to worrisome changes in this virus.

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Journal

Nature Biotechnology

DOI

10.1038/s41587-025-02636-6 

 

Reducing traffic in Barcelona by 25% would prevent around 200 premature deaths a year linked to pollution

A study assesses the impact that the Urban Mobility Plan and the electrification of the port could have on NO2 levels in the city and related mortality

Barcelona Institute for Global Health (ISGlobal)

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A 25% reduction in motorised traffic in the city of Barcelona would have significant health benefits. A study carried out by the Barcelona Institute for Global Health (ISGlobal), a centre supported by the "la Caixa" Foundation, estimates that this reduction in the number of vehicles could lead to a 17.6% reduction in nitrogen dioxide (NO2) levels. This improvement in air quality would prevent almost 200 premature deaths per year, and if the electrification of the port is completed, the number of avoidable deaths would rise to 228 per year.

The study, published in the journal Health & Place, has been carried out in collaboration with the Barcelona Supercomputing Center-Centro Nacional de Supercomputación (BSC-CNS), which has developed a technology that allows the modeling of traffic emissions and other sources throughout the city and the resulting pollution levels at the level of census tract, based on the evolution of a series of variables, including car activity, meteorology and urban geometry, among others.

Following the methodology used in health impact studies, the team established a baseline scenario set in 2019. From this, three hypothetical scenarios were established, each with different levels of traffic reduction but with one thing in common: the implementation of the 2018-2024 Urban Mobility Plan, which included measures such as the creation of superblocks and green corridors, the creation of a low-emission zone and tactical urban planning measures.

Same amount of traffic, but less polluting cars

For the first simulation, a conservative scenario was defined in which it was not possible to reduce the number of private vehicles in the city, but it was possible to remove the most polluting vehicles from circulation. In this case, the models estimated that there would be a 5.9% reduction in NO2 levels. This reduction would prevent 67 premature deaths related to nitrogen dioxide each year. The benefits associated with this scenario would be evenly distributed across the city.

25% fewer private cars on the road

The second scenario simulated a 25% reduction in the number of private cars on the road, resulting in a 17.6% reduction in NO2 concentrations and the prevention of 199 deaths per year. In this case, the reduction in mortality would be concentrated especially in the city centre, which is in fact the area with the highest pollution levels, as well as areas to the north-west.

The role of port electrification

The third scenario considered emissions from ports. It is estimated that maritime traffic contributes to around 7% of NO2-related mortality in the city. The Port of Barcelona currently has a plan to electrify its docks to reduce emissions from ships while they are in port, which is expected to be completed in 2030. Therefore, the combined impact of a 25% reduction in private traffic and the electrification of the port was simulated, resulting in a 19.4% reduction in NO2 levels and 228 preventable deaths per year. This combination of factors would be particularly beneficial in reducing mortality in the southern areas of the city, the ones closest to the coast.

The starting point for all the analyses was the city's mortality data supplied by the City Council and the NO2 levels for all the scenarios estimated by the models according to the variables introduced. The relationship between NO2 levels and the number of preventable deaths was obtained from previous studies.

Far from meeting European regulations

“Although the preventable mortality we estimate is significant, none of the scenarios proposed in our study would be able to comply with the new NO2 limits proposed by the European Union in its new air quality directive, which will come into force in 2030. This suggests that we must do more and do it more effectively in order to improve the air quality in our city,” says Ana Ramos, ISGlobal researcher and first author of the study.

Mark Nieuwenhuijsen, director of ISGlobal's Climate, Air Pollution, Nature and Urban Health programme, points out: “This study focuses on Barcelona, but it also sets an example for other cities to understand the impact that targeted policies can have on reducing air pollution.”

“The study focuses only on the impact of these measures on NO2 levels, but it is hoped that they will also have a positive effect on the climate in terms of reducing greenhouse gas emissions,” says Marc Guevara, leader of the atmospheric emissions modelling team at the BSC.

Reference

Ana Ramos Velásquez, Marc Guevara, Jan Mateu Armengol, Daniel Rodríguez-Rey, Natalie Mueller, Marta Cirach, Sasha Khomenko, Mark Nieuwenhuijsen, Health impact assessment of urban and transport developments in Barcelona: A case study, Health & Place, Volume 91, 2025, 103406, ISSN 1353-8292, https://doi.org/10.1016/j.healthplace.2024.103406.

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Journal

Health & Place

DOI

10.1016/j.healthplace.2024.103406 

Method of Research

Case study

Article Title

Health impact assessment of urban and transport developments in Barcelona: A case study