Publisher Health

A neurosurgeon, he helped develop an insulin pump for diabetes patients and a device to relieve pain, and joined Ben Carson in a historic operation on conjoined infants.Donlin M. Long, a pioneering neurosurgeon whose brain research helped millions of patients manage pain and who collaborated on the invention of an implantable pump to deliver insulin to people with diabetes, died on Sept. 19 near Gettysburg, Pa. He was 89.The cause was complications of a fall he suffered while fly-fishing for trout in a stream near his weekend home, his daughter Dr. Kimberly Page Riley said. Dr. Long was a resident of North Baltimore and chairman of the neurosurgery department at Johns Hopkins University for 17 years.In addition to the insulin pump, Dr. Long, as an expert in relieving chronic pain, also had a collaborative hand in introducing, in 1981, the first battery-powered, rechargeable, implantable electronic device to stimulate peripheral nerves to relieve pain, according to Johns Hopkins. The device, known as TENS, for transcutaneous electrical nerve stimulator, became a standard medical tool.As an accomplished practitioner of skull base surgery, Dr. Long was also instrumental in the first successful separation of twin infants born conjoined at the head. The operation, performed in 1987, involved 70 surgeons, nurses and assistants and lasted 22 hours.The twins’ brains were separated, and one of the infants’ skulls was closed by Dr. Benjamin S. Carson, whom Dr. Long, the founding chairman of the department of neurosurgery at Johns Hopkins University in Baltimore, had recruited to the university. The operation, at Johns Hopkins Hospital, brought Dr. Carson instant fame. He was later a Republican presidential candidate and secretary of the Department of Housing and Urban Development under President Donald J. Trump.Dr. Long, Dr. Carson’s mentor, closed the other boy’s skull during the operation.Drs. Long and Carson had just one hour to accomplish final separation, to reconstruct the divided brain cavities and veins, and to restart the hearts in the infants, both of them boys.Dr. Patrick J. Connolly, the chief of neurosurgery at Virtua Mount Holly Hospital in New Jersey and a professor at the Perelman School of Medicine at the University of Pennsylvania, hailed Dr. Long’s contributions to neurosurgery as well as to two other specialties, the treatment of vascular and spinal diseases.“We use steroids to treat brain edema every day in neurosurgery thanks to Dr. Long’s research in the early ’70s,” he said, “and his contribution to spinal cord stimulation has permitted relief of suffering for millions of people over the last 50 or so years.”When Dr. Long arrived at Johns Hopkins in 1973, the neurosurgery department had only five full time surgeons, performing some 125 surgeries a year. By the time he retired in 2000, the full-time staff had more than doubled and the number of operations had soared to more than 3,500 annually, performed at Johns Hopkins Hospital and Johns Hopkins Bayview Medical Center.He was instrumental in Johns Hopkins’ decision to erect the Adolf Meyer Center in 1981, uniting the departments of neurosurgery, neurology and psychiatry in one building and facilitating collaboration among them.Dr. Long’s research into chronic pain prepared him to help design the transcutaneous electrical nerve stimulator at Johns Hopkins. Later in the 1980s, he collaborated with colleagues at the Johns Hopkins Applied Physics Laboratory to invent the implantable medication pump to treat diabetic patients.Many of the surgeons trained during Dr. Long’s tenure at Johns Hopkins were hired as full professors, as leaders of neurosurgery departments at hospitals and universities, and as heads of professional associations.“Neurosurgeons everywhere stand on his shoulders,” Dr. Connolly said.Donlin Martin Long Jr. was born on April 14, 1934, in Rolla, Mo., in the southwest Ozarks. He was a descendant of New England Quakers, one of whom, according to a Johns Hopkins biography, had blazed a trail through the Cumberland Gap in the Appalachians alongside Daniel Boone. His father, Donlin Sr., was a chemist for the state health department. His mother, Davine (Johnson) Long, was a teacher.Raised in Jefferson City, Mo., Dr. Long earned undergraduate and medical degrees, in 1955 and 1959, from the University of Missouri. He received a doctorate in neuroanatomy in 1964 from the University of Minnesota, where he had planned to become a cardiac surgeon before changing course and focusing on neurosurgery, inspired by the work of Dr. Lyle A. French in that field.As residents at Minnesota, he and Joseph Galicich conducted research that led to the use of steroids to reduce postoperative brain swelling.Dr. Long told The New York Times in 1987 that “chronic pain is the weakest area of modern medicine and the least well managed of any complaint or disease.”He is survived by his wife, Harriett (Kallenbach) Long; another daughter, Elisabeth Merchant Long; a son, David; and four grandchildren. His three children have all taught or worked as administrators at Johns Hopkins.Remembered for his equanimity, his role as a mentor and his can-do passion, Dr. Long often told his children and grandchildren, “There is no try, only did and did not.”Bernard Mokam

The NewsMeta was sued by more than three dozen states on Tuesday for knowingly using features on Instagram and Facebook to hook children to its platforms, even as the company said its social media sites were safe for young people.Colorado and Tennessee led a joint lawsuit filed by 33 states in the U.S. District Court for the Northern District Court of California, saying Meta — which owns Facebook, Instagram, WhatsApp and Messenger — violated consumer protection laws by unfairly ensnaring children and deceiving users about the safety of its platforms. The District of Columbia and eight other states filed separate lawsuits on Tuesday against Meta with most of the same claims.In their complaint, the states said Meta had “designed psychologically manipulative product features to induce young users’ compulsive and extended use” of platforms like Instagram. The company’s algorithms were designed to push children and teenagers into rabbit holes of toxic and harmful content, the states said, with features like “infinite scroll” and persistent alerts used to hook young users. The attorneys general also charged Meta with violating a federal children’s online privacy law, accusing it of unlawfully collecting “the personal data of its youngest users” without their parents’ permission.“Meta has harnessed powerful and unprecedented technologies to entice, engage, and ultimately ensnare youth and teens,” the states said in their 233-page lawsuit. “Its motive is profit.”Meta said it was working to provide a safer environment for teenagers on its apps and has introduced more than 30 tools to support teenagers and families.“We’re disappointed that instead of working productively with companies across the industry to create clear, age-appropriate standards for the many apps teens use, the attorneys general have chosen this path,” the company said in a statement.The coordinated suit shows states are prioritizing the issue of children and online safety and combining legal resources to fight Meta.Francis Mascarenhas/ReutersWhy the Case MattersIt’s unusual for so many states to come together to sue a tech giant for consumer harms. The coordination shows states are prioritizing the issue of children and online safety and combining legal resources to fight Meta, just as states had previously done for cases against Big Tobacco and Big Pharma companies.“Just like Big Tobacco and vaping companies have done in years past, Meta chose to maximize its profits at the expense of public health, specifically harming the health of the youngest among us,” Phil Weiser, Colorado’s attorney general, said in a statement.Lawmakers around the globe have been trying to rein in platforms like Instagram and TikTok on behalf of children. Over the past few years, Britain, followed by states like California and Utah, passed laws that would require social media platforms to boost privacy and safety protections for minors online. The Utah law, among other things, would require social media apps to turn off notifications by default for minors overnight to reduce interruptions to children’s sleep.Regulators have also tried to hold social media companies accountable for possible harms to young people. Last year, a coroner in Britain ruled that Instagram had contributed to the death of a teenager who took her own life after seeing thousands of images of self-harm on the platform.Laws to protect the safety of children online in the United States, however, have stalled in Congress as tech companies lobby against them.“We’ve been warning about Meta’s manipulation and harming of young people from its start and sadly it has taken years to hold it and other companies like Google accountable,” said Jeffrey Chester, the executive director of consumer advocacy at the Center for Digital Democracy. “Hopefully justice will be served but this is why it’s so crucial to have regulations.”How the Investigation StartedStates began investigating Instagram’s potentially harmful effects on young people several years ago as public concerns over cyberbullying and teen mental health mounted.In early 2021, Facebook announced that it was planning to develop “Instagram Kids,” a version of its popular app that would be aimed at users younger than 13. The news prompted a backlash among concerned lawmakers and children’s groups.Soon after, a group of attorneys general from more than 40 states wrote a letter to Mark Zuckerberg, the company’s chief executive. In it, they said that Facebook had “historically failed to protect the welfare of children on its platforms” and urged the company to abandon its plans for Instagram Kids.Concerns among the attorneys general intensified in September 2021 after Frances Haugen, a former Facebook employee, leaked company research indicating that the company knew its platforms posed mental health risks to young people. Facebook then announced it was pausing the development of Instagram Kids.That November, a bipartisan group of attorneys general, including Colorado, Massachusetts and New Hampshire, announced a joint investigation into Instagram’s impact — and potential harmful effects — on young people.RemediesUnder local and state consumer protection laws, the attorneys general are seeking financial penalties from Meta. The District of Columbia and the states are also asking the court for injunctive relief to force the company to stop using certain tech features that the states contend have harmed young users.What Happens NextMeta is expected to fight to dismiss the case. Mr. Weiser, the Colorado attorney general, said in a news conference that he filed the lawsuit because he wasn’t able to reach a settlement with the company. He noted that Meta had filed a motion to dismiss a separate lawsuit filed by consumers, which accuses the company of similar allegations of harms toward children and teenagers.Separately, a group of attorneys general from more than 40 states is pursuing an investigation into user engagement practices at TikTok and their possible harmful effects on young people. That investigation, which was announced in 2022, is ongoing.

The INTERLACE phase III trial, funded by Cancer Research UK and UCL Cancer Trials Centre, assessed whether a short course of induction chemotherapy (IC) prior to chemoradiation (CRT) could reduce the rate of relapse and death among patients with locally advanced cervical cancer. As part of an analysis of clinical data, the preliminary results will be presented at the European Society for Medical Oncology (ESMO) congress on Sunday 22 October 2023.
The peak incidence of cervical cancer is in women in their early thirties, with around 3,200 new cases each year in the UK. CRT has been the standard treatment for cervical cancer since 1999, but despite improvements in radiation therapy techniques cancer returns in up to 30% of cases. The five-year survival rate for cervical cancer stands at around 70%.
Over the course of 10 years, 500 patients took part in INTERLACE at hospitals in the UK, Mexico, India, Italy and Brazil. Those who participated in the study had been diagnosed with cervical cancer, which was large enough to be seen without a microscope but had not yet spread to other parts of the body. The median age of patients in the trial was 46.
Patients were randomly allocated to receive either standard CRT (external radiation with weekly cisplatin and brachytherapy), or an initial six-week course of IC (carboplatin and paclitaxel chemotherapy) followed by the same standard CRT described above. After five years, 80% of those who received IC plus CRT were alive and 73% had not seen their cancer return or spread. In the standard treatment group, 72% were alive and 64% had not seen their cancer return or spread.
Dr Mary McCormack, lead investigator of the trial from UCL Cancer Institute and UCLH, said: “Our trial shows that this short course of additional chemotherapy delivered immediately before the standard CRT can reduce the risk of the cancer returning or death by 35%.
“This is the biggest improvement in outcome in this disease in over 20 years. I’m incredibly proud of all the patients who participated in the trial; their contribution has allowed us to gather the evidence needed to improve treatment of cervical cancer patients everywhere. We couldn’t have done this without the generous support of Cancer Research UK.”
Because the drugs required for IC, carboplatin and paclitaxel, are cheap, accessible and already approved for use in patients, the authors say they could be incorporated into standard of care treatment relatively quickly.

A research team from Osaka Metropolitan University has found that polysulfides are abundant in broccoli sprouts. They found that the amount of polysulfides increased dramatically during growth, by an approximately 20-fold in seeds by the fifth day of germination. Furthermore, a comprehensive analysis of the polysulfides detected a number of polysulfide candidates whose structures have not yet been determined. The identification of these unknown polysulfides and detailed analysis of their pharmacological activities are expected to enable the development of new preventive and therapeutic strategies and medicines for cancer, neurodegenerative diseases, stroke, inflammation, and other diseases.
Remember when your parents used to say, “Eat your greens, they are good for you”? Well, they were really onto something. Several studies have shown that higher intakes of cruciferous vegetables like broccoli, one of the most widely consumed vegetables in the United States, are associated with reduced risks of diseases such as diabetes and cancer, thanks to their organosulfur compounds, such as glucosinolates and isothiocyanates that exhibit a broad spectrum of bioactivities including antioxidant activity. However, few studies have focused on the endogenous content of polysulfide in broccoli sprouts.
A research team led by Assistant Professor Shingo Kasamatsu and Professor Hideshi Ihara of the Graduate School of Science at Osaka Metropolitan University, investigated the amount of polysulfides in broccoli sprouts during the process of their germination and growth. Building upon their previous work, where the research team demonstrated the abundance of polysulfide molecules in cruciferous vegetables.
The team found that total polysulfide content in broccoli sprouts significantly increased during germination and growth, with an approximately 20-fold increase in polysulfides on the fifth day of germination. Furthermore, they discovered a number of unknown polysulfides with indeterminate molecular structures. These findings suggest that the abundance of polysulfides in broccoli sprouts may contribute to their well-known health-promoting properties.
Dr. Kasamatsu stated, “The discovery of the significant increase in polysulfide content during the sprouting process from broccoli seeds was completely by chance and very surprising. This finding suggests that polysulfides may play an important role in the process of plant germination and growth. Further investigation of the pharmacological function of these unknown polysulfides could lead to the development of new preventive and therapeutic approaches and medicines for neurodegenerative diseases, stroke, cancer, inflammation, and other oxidative stress-related diseases.”

In a meta-study, a research team from the Institute of Environmental Biotechnology at TU Graz has provided evidence that the consumption of fruit and vegetables contributes positively to bacterial diversity in the human gut.
Bacterial diversity in the gut plays an important role in human health. The crucial question, however, is where are the sources of this diversity? It is known that an important part of the maternal microbiome is transferred to the baby at birth, and the same happens during the breastfeeding period via breast milk. Further sources were yet to be discovered. However, a team led by Wisnu Adi Wicaksono and Gabriele Berg from the Institute of Environmental Biotechnology at Graz University of Technology (TU Graz) has now succeeded in proving that plant microorganisms from fruit and vegetables contribute to the human microbiome. They report this in a study published in the journal Gut Microbes.
You are what you eat
The authors were able to demonstrate that the frequency of fruit and vegetable consumption and the variety of plants consumed influences the amount of fruit- and vegetable-associated bacteria in the human gut. Early childhood in particular represents a window of opportunity for colonisation with plant-associated bacteria. It was also demonstrated that the microorganisms of plant origin have probiotic and health-promoting properties.
A microbiome is the totality of all microorganisms that colonise a macroorganism (human, animal, plant) or a part of it, for example the intestine or a fruit. While the individual microbiomes are becoming better understood, little is known about their connections. “The proof that microorganisms from fruits and vegetables can colonise the human gut has now been established for the first time,” explains first author Wisnu Adi Wicaksono. This suggests that the consumption of fruit and vegetables, especially in infancy, has a positive influence on the development of the immune system in the first three or so years of life, as the intestinal microbiome develops during this time. But even after that, a good diversity of gut bacteria is beneficial for health and resilience. “It simply influences everything. Diversity influences the resilience of the whole organism; higher diversity conveys more resilience,” says Institute head Gabriele Berg.
Several billion sequences
In order to be able to determine that the consumption of fruits and vegetables and their microbiomes actually leads to changes in the intestinal microbiome, the team first created a catalogue of microbiome data from fruits and vegetables which enabled them to assign their bacteria. They compared these with publicly available data from two studies on intestinal flora. The TEDDY project looked at the development of babies in a long-term study and the American Gut Project studied the intestinal microbiome of adults — both projects also collected data on the food intake of the test persons. In total, the researchers had metagenome data from around 2500 stool samples at their disposal, each of which contained between one and ten million sequences — several billion sequences were thus evaluated. Using this extensive data set, the presence of fruit and vegetable microflora in the gut could be demonstrated. This evidence is a crucial building block in proving the WHO’s One Health concept, which closely links human, animal and environmental health.
Follow-up study on three continents
To further explore this connection, together with international colleagues and within the EU-funded HEDIMED project Gabriele Berg at the Institute of Environmental Biotechnology is already working on an intervention study in which people on three continents eat exactly the same things for a certain period of time, following which their excretions are analysed. But even beyond that, Gabriele Berg sees many areas that could be influenced on the basis of the study’s findings. This starts with food production, as soil, fertiliser and pesticides affect the plant microbiome. “Fresh fruit and vegetables will always have the best microbiome; agriculture or processing companies already have a major influence here. And the storage and processing of food must also be critically reconsidered,” explains Berg. Depending on the findings of the planned study, there could also be exciting applications for individuals. “Every fruit and vegetable has a unique microbiome. So maybe at some point a personalised diet can be put together based on that.”

Scientists at The University of Toledo have proven that engineered bacteria can lower blood pressure, a finding that opens new doors in the pursuit of harnessing our body’s own microbiome to treat hypertension.
The study, published this month in the peer-reviewed journal Pharmacological Research, represents a paradigm shift, said Dr. Bina Joe, a hypertension researcher at UToledo and the paper’s senior author.
“The question we always ask is, can we exploit microbiota to help our health, for which optimal blood pressure is a cardinal sign. Until now, we have simply said changes in microbiota play a role in elevated blood pressure or hypertension. Those are important findings, but they don’t always have an immediately translational application,” she said. “This is the first time we have shown that we really can do this. It’s a proof of principle that you can use microbiota to make products that measurably improve your health.”
Joe, a Distinguished University Professor and chair of the Department of Physiology and Pharmacology in the UToledo College of Medicine and Life Sciences, is a pioneer in studying the connection between bacteria living in our gut and blood pressure regulation.
In her most recent research, Joe and her team tested Lactobacillus paracasei, a beneficial gut bacterium, that was specially modified to produce a protein called ACE2 in lab rats that are predisposed to hypertension and unable to naturally produce ACE2.
ACE2 has drawn considerable interest in recent years because of its role as a key receptor for the virus that causes COVID-19.
However, the protein also negatively regulates the renin-angiotensin system which generates angiotensin II, a hormone that raises blood pressure in a number of ways, including by the constriction of blood vessels.

Automated insulin delivery should be rolled out to pregnant women with type 1 diabetes — according to researchers at the University of East Anglia.
The technology — known as ‘hybrid closed-loop technology’ — gives insulin doses as informed by a smartphone algorithm.
A new study published today shows that the move could help pregnant women better manager their blood sugars compared to traditional insulin pumps or multiple daily injections.
Lead researcher Prof Helen Murphy, from UEA’s Norwich Medical School, said: “Despite better systems for monitoring blood sugars and delivering insulin, altered eating behaviours and hormonal changes during pregnancy, mean that most women struggle to reach the recommended blood sugar targets.
“This means that complications related to having type 1 diabetes during pregnancy are widespread, affecting one in every two new-born babies.
“For the baby, these include premature birth, need for intensive care after birth, and being too large at birth, which increases the lifelong risk of overweight and obesity. Low blood sugars, excess weight gain, and high blood pressure during pregnancy are common amongst mothers.
“We wanted to investigate how automated insulin delivery could help.”
The teamtrialled a technology known as Hybrid Closed-Loop or Artificial Pancreas. It consists of an algorithm which sits on a smartphone and communicates with the traditional continuous glucose monitoring and insulin pump systems.

Mount Sinai researchers have discovered a link between certain per- and polyfluoroalkyl substances (PFAS) and an increased risk for thyroid cancer, according to a study published in eBioMedicine today.
PFAS, also known as “forever chemicals,” are a large, complex group of synthetic chemicals that can migrate into the soil, water, and air. Due to their strong carbon-fluorine bond, these chemicals do not degrade easily in the environment. Forever chemicals been used in consumer products around the world since the 1940s, including nonstick cookware, water-repellent clothing, stain-resistant fabrics, and other products that resist grease, water, and oil.
Multiple national and international institutions, including the European Parliament and the U.S. Environmental Protection Agency (EPA), have declared PFAS exposure a health crisis. This study supports the actions needed to regulate and remove these chemicals from potential exposure routes. Although PFAS exposure has been identified as a potential contributor to recent increases in thyroid cancer, limited studies have investigated the association between PFAS exposure and thyroid cancer in human populations.
“With the substantial increase of thyroid cancer worldwide over recent decades, we wanted to dive into the potential environmental factors that could be the cause for this rise. This led us to the finding that PFAS, ‘forever chemicals,’ may at least partially explain the rise of thyroid cancer and are an area we should continue to study further,” said co-corresponding author Maaike van Gerwen, MD, PhD, Assistant Professor and Director of Research for the Department of Otolaryngology — Head and Neck Surgery, Icahn School of Medicine at Mount Sinai. “Thyroid cancer risk from PFAS exposure is a global concern given the prevalence of PFAS exposure in our world. This study provides critical evidence to support large-scale studies further exploring the effect of PFAS exposure on the thyroid gland.”
The researchers investigated associations between plasma PFAS levels and thyroid cancer diagnosis using BioMe, a medical record-linked biobank at Icahn Mount Sinai. They studied 88 thyroid cancer patients with plasma samples collected either at or before cancer diagnosis and 88 non-cancer controls — people who did not develop any form of cancer — who matched on sex, race/ethnicity, age (within five years), body mass index, smoking status, and the year of sample collection. The researchers measured levels of eight PFAS in blood samples from the BioMe participants using untargeted metabolomics. The levels of individual PFAS were compared between the group of participants who developed thyroid cancer and the group of healthy participants, using different statistical models to estimate accuracy.
The results showed that exposure to perfluorooctanesulfonic acid (n-PFOS, a group of chemicals under the PFAS umbrella) led to a 56 percent increased risk of thyroid cancer diagnosis. Additionally, the researchers conducted the analysis again in a subgroup of 31 patients who had at least a year between their enrollment in BioMe and their diagnosis of thyroid cancer, to take into consideration the time lag between exposure to PFAS chemicals and developing a disease. From this second analysis, there was also a positive association between the exposure of n-PFOS and the risk of thyroid cancer, as well as a positive association with a few additional PFAS chemicals, including branched perfluorooctanesulfonic acid, perfluorononanoic acid, perfluorooctylphosphonic acid, and linear perfluorohexanesulfonic acid.
“The results of this study provide further confirmation for the PFAS health crisis and underline the need to reduce, and hopefully one day eliminate, PFAS exposure,” said co-corresponding author Lauren Petrick, PhD, Associate Professor of Environmental Medicine and Public Health, Icahn Mount Sinai. “Today, it’s nearly impossible to avoid PFAS in our daily activities. We hope these findings bring awareness of the severity of these forever chemicals. Everyone should discuss their PFAS exposure with their treating physician to determine their risk and get screened if appropriate. In addition, we need continued industry changes to eliminate PFAS altogether.”
This study was funded with pilot funding through the Department of Environmental Medicine and Public Health and the Institute for Exposomic Research’s National Institute of Environmental Health Sciences-funded Center on Health and Environment Across the LifeSpan (HEALS), which supports research on environmental exposures, and their effects on health across the life course.

Engineers at the University of California San Diego have developed a smartphone attachment that could enable people to screen for a variety of neurological conditions, such as Alzheimer’s disease and traumatic brain injury, at low cost — and do so accurately regardless of their skin tone.
The technology, published in Scientific Reports, has the potential to improve the equity and accessibility of neurological screening procedures while making them widely available on all smartphone models.
The attachment fits over a smartphone’s camera and improves its ability to capture clear video recordings and measurements of the pupil, which is the dark center of the eye. Recent research has shown that tracking pupil size changes during certain tasks can provide valuable insight into an individual’s neurological functions. For example, the pupil tends to dilate during complex cognitive tasks or in response to unexpected stimuli.
However, tracking pupil size can be difficult in individuals with dark eye colors, such as those with darker skin tones, because conventional color cameras struggle to distinguish the pupil from the surrounding dark iris.
To enhance the visibility of the pupil, UC San Diego engineers equipped their smartphone attachment with a specialized filter that selectively permits a certain range of light into the camera. That range is called far-red light — the extreme red end of the visible spectrum located just before infrared light. Melanin, the dark pigment in the iris, absorbs most visible wavelengths of light but reflects longer wavelengths, including far-red light. By imaging the eye with far-red light while blocking out other wavelengths, the iris appears significantly lighter, making it easier to see the pupil with a regular camera.
“There has been a large issue with medical device design that depends on optical measurements ultimately working only for those with light skin and eye colors, while failing to perform well for those with dark skin and eyes,” said study senior author Edward Wang, an electrical and computer engineering professor in The Design Lab at UC San Diego, where he is the director of the Digital Health Technologies Lab. “By focusing on how we can make this work for all people while keeping the solution simple and low cost, we aim to pave the way to a future of fair access to remote, affordable healthcare.”
Another feature of this technology that makes it more accessible is that it is designed to work on all smartphones. Traditionally, pupil measurements have been performed using infrared cameras, which are only available in high-end smartphone models. Since regular cameras cannot detect infrared light, this traditional approach limits accessibility to those who can afford more expensive smartphones. By using far-red light, which is still part of the visible spectrum and can be captured by regular smartphone cameras, this technology levels the playing field.

Gene therapy currently represents the most promising approach for the treatment of hereditary diseases. Yet despite significant breakthroughs in recent years, there are still a number of hurdles that hinder the wider application of gene therapies. These include the efficient delivery of genetic material into target cells with minimal side effects using adeno-associated viral vectors (AAVs). The AAV carrier substances have an advantageous safety profile and high gene transfer efficiency, meaning they are often used in gene therapies and in gene editing with CRISPR/Cas. But, AAVs have limited DNA uptake capacity and cannot reliably transport larger genes.
In the past, various methods have been developed to circumvent these drawbacks. Such methods rely on splitting the coding DNA into two fragments that contain the ability to be rejoined in the target tissue. The disadvantage of these strategies, however, is that they are not very efficient and offer less flexibility for experimental design, as well as causing potential side effects.
Assembly at transcript level
The team of Elvir Becirovic, professor of experimental and translational opthalmology at the University of Zurich, has now developed a novel approach to circumvent these drawbacks. This new method, called REVeRT (reconstitution via mRNA trans-splicing), also uses the principle of dual AAV vectors. However, unlike previous technologies, it relies on the assembly of split gene fragments at the transcript level.
“The advantages of this method are increased efficiency and fewer side effects,” explains Becirovic. “It is also more flexible than previous methods, as the large genes can be divided into two fragments at various points.” His team has also developed the method for opthalmologic applications in cell cultures and successfully evaluated it in animal models under various conditions, for example to treat hereditary macular degeneration with gene therapy.
Possible therapies for various diseases
REVeRT is also suitable for use in gene therapies for other genetic or acquired diseases — such as various common blood disorders or diseases associated with aging. The new method can also find application in gene therapy studies using CRISPR/Cas genome editing. For such modules to be of therapeutic use, the coding DNA needs to be transferred into the target cells as efficiently as possible with the help of carriers such as AAVs. “With CRISPR/Cas further applications are possible, opening up new treatment options,” says Becirovic.