Category Archives: Human Genetic Engineering

Data support the initiation of an upcoming first-in-human trial for first-line, MRD+ multiple myeloma patients post-ASCT

NEW HAVEN, Conn., May 15, 2020 (GLOBE NEWSWIRE) -- Kleo Pharmaceuticals, Inc., a leading company in the field of developing next-generation, fully synthetic bispecific compounds designed to emulate or enhance the activity of biologics, today announced preclinical data for the companys lead program, KP1237 in combination with autologous, cytokine-induced, memory-like (CIML) natural killer (NK) cells with low dose IL-2 in multiple myeloma (MM). KP1237 is a CD38-targeting antibody recruiting molecule (ARMTM). These data, to be presented as a poster at the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting being held May 2931, will support the initiation of an upcoming Phase 1/2 clinical trial for MM patients receiving an autologous stem cell transplant (ASCT), who remain minimum residual disease positive (MRD+)

This research, in collaboration with Dr. Rizwan Romee, Director of the Haploidentical Donor Transplantation Program at the Dana Farber Cancer Institute, will be presented as a poster and highlight the activity of the combination of KP1237 with CIML NK cells against CD38-expressing MM target cells. Several in vitro and ex vivo experiments show how KP1237 targets the NK cell therapy to the tumor cells and increases their cytotoxicity. These data led to the clinical exploration of this combination product in the high unmet medical need population of multiple myeloma patients who are MRD+ pre-ASCT.

These data mark an important milestone for the ARM platform as we advance towards the first clinical trials for our growing company, said Doug Manion, Kleos Chief Executive Officer and Chairman of the Board. Initiation of these trials will allow us to demonstrate clinical proof of concept and, ultimately, facilitate the expansion of our technology platforms across indications. Additionally, this milestone moves us closer to our primary goal of having a meaningful impact on patient survival and quality of life.

ARMs are unique, bispecific molecules composed of two active ends connected by a linker. One of the ends binds to a target molecule on a cancer cell, while the other end can bind to and thus recruit all endogenous IgG antibodies circulating in the body, which then bind to and activate NK cells. Therefore, ARMTM molecules behave similarly to chimeric antigen receptors to target immune cells to tumors, though their synthetic nature eliminates the need for genetic engineering of the cells. KP1237, by targeting CD38 expressed on the surface of multiple myeloma cells, facilitates NK-cell mediated killing of these tumor cells. The modular design enable ARMTM molecules to be broadly applicable as targeting tolls for all types of NK cell products across a range of tumor types.

Details of the poster presentation are as follows:

Title: A first-in-class ex vivo combination between cytokine-induced memory like (CIML) NK cells and a CD38 targeting antibody recruiting molecule (ARM) as a novel approach to target NK cells without cellular engineering for the treatment of multiple myeloma.Session: Hematologic MalignanciesPlasma Cell DyscrasiaAbstract: #8523

This ASCO abstract is now available at https://meetinglibrary.asco.org/record/187657/abstract. The poster presentation will include additional data not available in the abstract.

About Kleo Pharmaceuticals, Inc.

Kleo Pharmaceuticals is a unique biotechnology company developing next-generation, bispecific compounds designed to emulate or enhance the activity of biologics based on the groundbreaking research of its scientific founder Dr. David Spiegel at Yale University. Kleos compounds are designed to direct the immune system to destroy cancerous or virally infected cells and are currently in development for the treatment of various diseases, including multiple myeloma and COVID-19. Compared to biologics, Kleos compounds are smaller and more versatile, leading to potentially improved safety and efficacy. They are also much faster and more efficient to design and produce, particularly against novel targets. Kleo develops drug candidates based on its proprietary technology platforms, all of which are modular in design and enable rapid generation of novel immunotherapies that can be optimized against specified biological targets and combined with existing cell- or antibody-based therapies. These include Antibody Recruiting Molecules (ARMs) and Monoclonal Antibody Therapy Enhancers (MATEs). Biohaven Pharmaceutical Holding Company (BHVN) and PeptiDream Inc. (PPTDF) are investors in Kleo Pharmaceuticals. For more information visit http://kleopharmaceuticals.com.

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Forward-Looking StatementsThis news release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements involve substantial risks and uncertainties, including statements that are based on the current expectations and assumptions of the Company's management. All statements, other than statements of historical facts, included in this press release regarding the Company's plans and objectives, expectations and assumptions of management are forward-looking statements. The use of certain words, including the words "estimate," "project," "intend," "expect," "believe," "anticipate," "will, "plan," "could," "may" and similar expressions are intended to identify forward-looking statements. The forward-looking statements are made as of this date and the Company does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

CONTACT INFORMATION

LifeSci Advisors (Investors)

Irina Koffler

646-970-4681

ikoffler@lifesciadvisors.com

Kleo Pharmaceuticals (Press)

Brian Dowd, PhD

203-390-9375

bdowd@kleopharmaceuticals.com

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Kleo Pharmaceuticals to Present Preclinical Data Highlighting the Synergistic Potential of Kleo Asset KP1237 and Autologous NK Cells in the Treatment...

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A new report from the US Government Accountability Office (GAO) has given insight into how the cell based meat industry is stuck in its R&D phase. The report demonstrates that there is still plenty of mystery in the fledgling industry, as food tech competes to premier and dominate the market from the onset.

The GAO states: Specific information about the technology being used, eventual commercial production methods, and composition of the final products are not yet known. It has found that the technology and methods are still in development and said FDA and USDA do not have clarity about whats going on with the secretive R&D projects.

The report cites the following issues, which we have summarized, as needing further clarity:

Many questions of course remain to be answered at this stage and vegconomist will keep you informed of developments. Although it is still debatable as to how vegan cultured meat really is, it clearly has the potential to drastically reduce the devastating impact of traditional animal farming, and remove animals from the food system.

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GAO report Highlights Barriers in Getting Cell Based Meat to Market - vegconomist - the vegan business magazine

Currently more than 80 countries have expressed interest in acquiring Heberon. Photo: CIGB

Since the appearance, March 11, of the first cases of COVID-19 in Cuba, the countrys Ministry of Public Health (Minsap) has reported that the inclusion of Recombinant Human Interferon Alpha 2b in treatment protocols for these patients has shown positive results.

Details on the effectiveness of the product were presented by Dr. Eulogio Pimentel Vzquez, director of the Center for Genetic Engineering and Biotechnology (CIGB), affiliated with the BioCubaFarma Enterprise Group, where the medication was first produced in the late 1980s.

"The strength of the Cuban health system, and its close ties with the biotechnology and pharmaceutical industries, in our social system that prioritizes the people's health, makes possible the medications availability for all Cubans."

According to Dr. Pimentel, in accordance with the Minsap treatment protocol, this product, in combination with other drugs, is used as soon as a case is confirmed, and not with patients in serious or critical condition.

Data released April 14 shows that 93.4% of patients testing positive for SARS-COV-2 had been treated with Heberon (the commercial name of Recombinant Human Interferon Alpha 2b). Only 5.5% reached serious condition. The mortality rate reported by Minsap on that date was 2.7%, while for patients with whom the drug was used, the rate was 0.9%. On this same date, on the international level, 15 to 20% of patients were reported in serious condition, while the mortality rate was over 6%.

"The data shows that the protocol in our country is effective, and interferon plays a key role in these results."

Referring to the medications use around the world, the doctor noted that important reports of preclinical and clinical evidence have appeared in several countries. One recent scientific article refers to a study conducted in Wuhan, China, regarding its use with medical personnel. Of the individuals included in the study, 2,944 received the drug and 3,387 did not. Fifty percent of those not treated contracted the disease, while there were no cases identified among those who benefited from Cuban interferon.

At this time, more than 80 countries have expressed interest in acquiring Heberon, reflecting confidence in its usefulness in confronting the pandemic.

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Cuban interferon proven effective against COVID-19 Cuba Granma - Official voice of the PCC - Granma English

The secret to predicting viral outbreaks like COVID-19 might be in our sewers. A Michigan State University researcher is spearheading a study to determine if viral outbreaks can be identified and forecasted through wastewater sampling.

Funded by the Great Lakes Water Authority, MSUs Irene Xagoraraki is using a method from one of her recently completed studies to test and predict COVID-19 in Detroit that can deliver warnings of potential outbreaks even before they appear in health facilities.

If our prediction models are showing early warning signals of a problem, we could sound the alarm for state and federal authorities to prepare for an outbreak, said Xagoraraki, associate professor in environmental engineering at MSU. The medical community needs to be armed with resources to help these communities and early action might be one of the answers.

For the initial study, funded by the National Science Foundation, Xagoraraki evaluated human viral pathogens excreted by the Detroit population that were collected from untreated wastewater samples between November 2017 to February 2018.

We developed two models; the first, a viral identification model, or Viral-ID, determines diversity and genetic makeup of viral infections in a certain population at a particular point in time, Xagoraraki said. The second, a viral prediction model, or Viral-PD, provides early signals of fluctuations of target viral diseases, such as hepatitis, COVID-19 and others, in certain geographical areas over time.

Using Viral-ID in the untreated wastewater, Xagoraraki was able to identify a number of enteric, respiratory, bloodborne and vector-borne viruses ranging from norovirus to human herpesviruses 8 (Kaposis sarcoma associated herpesvirus), the latter attributed to an HIV-AIDS outbreak in Detroit during the sampling period. Genetic sequences of multiple reported viral-related diseases in the Detroit population during the sampling period, found in clinical records reported by the state, were found in wastewater.

When testing the Viral-PD model, concentrations of hepatitis A in wastewater along with multiple other parameters were correlated with clinical data.

Increases in hepatitis A incidence in the surrounding community were revealed in wastewater approximately seven to nine days before cases were detected and reported by health care facilities, Xagoraraki said.

With the success of her first phase of research, Xagoraraki and her team are collecting samples weekly and measuring concentrations of beta coronavirus SARS-CoV2 (known as the novel coronavirus, or COVID-19) in wastewater. Assisting are MSU doctoral candidates Brijen Miyani and Camille McCall; recent graduates Huiyun Wu and Evan OBrian; and the Great Lakes Water Authority and the Detroit Water and Sewerage Department.

Xagoraraki said a critical component of genetic testing in environmental samples is concentrating and cleaning a sample to remove chemical or microbial contamination typically not found in a clinical sample.

To estimate virus detention times in the sewer collection network, hydrological and other network data are analyzed and modeled; to estimate contributing population, biomarkers and excreted metabolites are measured. Population health data and COVID-related characteristics, such as incubation times and shedding rates, are being collected and modeled to estimate delays between measured viral concentrations in wastewater and appearance of disease symptoms.

Results from Xagorarakis initial study can be seen in One Health, Water Research and Journal of Environmental Engineering.

If the predictive capability is validated for SARS-CoV-2, this method might provide a means to mitigate the current pandemic by enabling public health officials to act before an outbreak spreads farther, enabling the economy to stay open longer in the absence of expensive and time consuming massive testing, said John Verboncoeur, associate dean for research in the College of Engineering. In the longer term, this method might provide an early warning system to limit the effects of an emerging epidemic before it gets started, with multiple sites providing a spatiotemporal picture of the early spread of pathogens at low cost.

Xagoraraki is also working with the Institute for Global Health in the MSU College of Osteopathic Medicine to extend this to international locations.

According to Xagoraraki, this international work is critical as underserved populations in developing countries often dont seek or have access to medical care and outbreaks often go undetected. In such locations, in addition to centralized wastewater sampling, the team plans to include watershed sampling in critical locations to assess the viral load and viral diversity of the portion of the population that is not serviced by public utilities.

The implications for being able to detect viral shedding in wastewater before outbreaks of illnesses could guide future public health and public policy decisions related to epidemics and pandemics in these developing countries, said William Cunningham, associate dean for global health in the College of Osteopathic Medicine.

Everything were doing is at the research-level at this point however, it could be part of a larger solution across the country and world, Xagoraraki said. Our models are expected to describe patterns of endemic disease, identify potential novel viruses, and predict hot spots and critical moments for the onset or spread of outbreaks prior to full-blown demonstration of disease.

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Wastewater may help predict the next COVID-19 outbreak - MSUToday

The recent exchanges on Ethiopias acceptance of genetically modified (GM) crops and the resulting report of USDA praising the steps our country has taken continue to be informative. My understanding of the debates surrounding GM foods suggests that neat explanations about their usefulness grossly disregard the muddy footprints and messy stories of the technology while the voices of vilification and blanket rejection tend to thrive more on emotional appeal than rigorous science. Lets start with the basics.The 21st century is said to be the century of biology and ecology. Thus, for Ethiopia, as one of the globes top 50 centers of biodiversity, where better to capitalize on than in understanding and developing its crop and animal varieties and fulfill its long-held potential of being Africas breadbasket. Ethiopia is one of the few centers where domestication of crops was practiced at the dawn of agriculture and the country has contributed to the worlds collection of cultivable species such crops as Teff, coffee, enset, sorghum, millet, etc. It means that our farmers are not new to the genetic modification of organisms since every domestication effort involves selective breeding and recombination of desired characteristics. We also have adopted several foreign plant species (maize, wheat, barley, tomatoes, potatoes, pepper, etc.) some of them only a few centuries ago, without much consideration for their effects on our indigenous species.Despite these impressive records, our agricultural system stayed firmly rooted in its ancient practices which suffer from abysmal efficiency and very poor productivity. As a result, Ethiopia remains a net importer of crops both for human consumption and for its expanding industries, and there seems to be no natural end to this depressing trend. The consequence is not only a shrinking of profit base for many of the industries but also the misplaced use of the meager hard currency obtained from the export of some raw materials with all the negative impacts on our capacity in importing more useful technologies.

Ironically, Ethiopia has no shortage of cultivable/irrigable land or population able or willing to participate in modern agricultural practices. In fact, Ethiopias farming community is estimated to be above 80% of the population but is unable to feed itself properly let alone supply raw materials for the manufacturing sector. The production by small scale farmers in Ethiopia is demonstrably incapable of keeping pace with the population growth as tens of millions of our people still depend on food handouts every single year and many more live in precarious situations. Therefore, it is pertinent that the country becomes self-sufficient at least for feeding the population with all possible means. And, this is not a very hard task given the scale of its cultivable land and the disproportionately large population whose livelihood is dependent on farming.The most relevant question is thus how to end this absurdity and persistent tragedy without drastically affecting the livelihood of our farmers and disrupting the biodiversity balance. For a very long period of time, Ethiopia lacked the capacity to introduce mechanized farming and other relevant agricultural technologies. Further, it lagged far behind many (African) countries in developing its policies and relevant practices with regard to the application of plant genetic engineering technology. Arguably the most unhelpful effort on part of the Ethiopian government in the last decade has been the introduction of the Biosafety Proclamation No. 655/2009. It is possible that this proclamation was enacted as a genuine effort to protect the local farmers and the countrys agriculture sector from control by a few foreign biotech industries and create a formidable safeguard against potential fallouts from untended consequences of releasing GM crops. However, it is clear from the outset that the proclamation lacked proper scrutiny by all the relevant stakeholders, not least farmers representatives or experts from agricultural research centers in the country. In addition, it failed to recognize the potential of local agro-biotechnology research and innovation and was oblivious to the rapidly changing focus of the debate and policy shifts surrounding this emerging technology from around the world. Thus, our Biosafety Proclamation No. 655/2009 was, by international standards, relatively outdated as soon as it was hastily passed by the parliament (hence the justification for a later amendment as Proclamation No. 896/2015).It is unclear why modern GM organisms are so divisive and treated as highly toxic materials that should be feared and avoided at all costs. Rigorous analysis done by scientific institutions such as the UK Royal Society and the U.S. National Academy of Sciences has demonstrated that such organisms are at least as safe as their counterparts produced by conventional breeding techniques. For example, the GM cotton that Ethiopia is said to have started cultivating is the widely known Bt variety. In short, Bt is abbreviated from Bacillus thuringiensis, a bacterium species that naturally occurs in soil and produces highly specific insecticidal proteins. This bacterium has been in use, in one form or another, as the most effective, naturally occurring, and environmentally friendly bioinsecticide for more than half-century. Bt spray is currently the dominant bioinsecticide in the world and is authorized for use even by organic farmers worldwide. Therefore, we are talking about a well-characterized gene of a bacterium (which might as well be dwelling in our soils all along). Plants expressing this gene have been tested for more than two decades in several countries and in a wide range of ecological settings for the properties they have been designed for, with no confirmed case of ill effect as food or feed.I suspect that Ethiopia has been misled or pressured into adopting an overly cautious interpretation of the precautionary principle as was the case in the past in some EU countries. In my opinion, the EU and its policies on GM products (even as progressive as they currently are) cannot be a good lead for Ethiopia. For one, farming practices in the EU are already highly productive even without the need for the introduction of GM. In addition, the sheer proportion of the population involved in the agricultural sector in Ethiopia means that unreasonable restrictions on agricultural biotechnology can have far-reaching consequences. For Ethiopia, the better place to look for inspiration is other developing countries around the world in Latin America, Asia, and in the continent of Africa itself for our capacities and needs are likely to be similar.

India, for example, started commercial farming of Bt-cotton in 2002 and at the moment, about 25% of its agricultural land is covered with this variety, the highest proportion in the world. In our continent, South Africa is the pioneer in providing permits for the commercial cultivation of GM crops for GM cotton and maize starting in 1997. Egypt has been commercially farming Bt-maize hybrid since 2008, using seeds procured from South Africa (it has since suspended the cultivation due to the lack of proper biosafety laws and other local issues). Ghana, Nigeria, Cameroon, and, our neighboring countries, Sudan, Kenya, Uganda, Tanzania, and Mozambique have all tested and/or adopted the cultivation of GM crops. Furthermore, Nigeria, Kenya, and Uganda are pursuing various genetic modifications to the cassava plant, a staple crop for over half a billion people around the world. It is disingenuous, to say the least, to assert that all of these countries are either threatened or duped into accepting this technology to the detriment of the wellbeing of their population and ecosystems.Ethiopia, on the other hand, despite having several, experienced agricultural research institutions, is missing out for far too long on the development of its genetic research capacity and utilization of available biotechnologies, especially as compared to many of these African countries. As a commentary on this site made it clear, the Ethiopian team negotiating the Cartagena Protocol, led by Dr. Tewolde-Birhan Gebre-Egziabher, played a key role in formulating a strong African position and had become the continents de-facto representative. This had been appreciated and acknowledged by several African countries at that time. Whether this fact can make Ethiopia assume a Pan-Africanist leadership position in the environmental issues is completely irrelevant to the issue at hand. What is important is the fact that the Cartagena Protocol aims mainly to provide an adequate level of protection to worldwide biodiversity by placing a stringent control on the transboundary movement, transit, handling and use of all living modified organisms that may have adverse effects on the conservation and sustainable use of biological diversity. What it is not is an outright ban on the development, test or use of GM organisms for food or feed. In addition, several of the major African countries have since moved on and have come to realize that application GM crops, transgenic technology, and genetic engineering know-how could have a transformative effect on parts their economies provided that these are supported by a strong monitoring regimen. As a result, and contrary to its supposed pan-African leadership, Ethiopia is currently an outlier in the continent when it comes to the exploration of this powerful technology that can potentially transform the living standards of millions of people. Many of the countries that are said to be hesitant in accepting this agricultural biotechnology lack either the capacity to adapt and manage it or the actual need for a rapid transformation of their agricultural practices (they are either food self-sufficient or have no industrial base to supply to or both). In other words, we may as well have once been the continents leading voice against GM organisms but it has become apparent that we are leading the wrong league and it is not where we belong it is unbecoming to our great nation.What Ethiopia urgently needs is a dynamic regulatory system and strong scientific capacity for the evaluation, authorization, and monitoring of imported GM crops. It also needs to rebuild and expand its capability for fundamental research with the aim of developing local GM species using state-of-the-art methodology. Public-private biotechnology partnerships should be encouraged to work on genetic identification and improvements even in our own indigenous species of plants and animals. Furthermore, since we are negotiating for accession to the World Trade Organization, it is the most relevant time to substantially revise or repeal the Biosafety Proclamation No. 655/2009 (including its latest incarnation, Proclamation No. 896/2015) and streamline other relevant laws in accordance with international standards.

To this writer, the question is not to be why Ethiopia allowed the commercial cultivation of Bt-cotton and has authorized a confined field trial of Bt-maize. It is whether it had conducted a thorough analysis of the existing problems in the sector and identified the effectiveness of these particular strains of GM crops as cost-effective and sustainable solutions. It is not a case of re-inventing the wheel but of identifying our desirable targets and requirements, learning from the front-runners, and applying an appropriate level of precautionary principles. The temporary setbacks in Burkina Faso, Africas largest producer of cotton at one point, and some regions in India demonstrate that the process of introducing GM crops is far from being a turn-key situation. It requires the collaboration of laboratory scientists, policymakers, market leaders, and farmers (end-users) in identifying the required crop characteristic and quality that is suitable for the specific condition of the locality.In conclusion, agricultural gene-modification technology has sufficiently demonstrated its worth after more than two decades of commercial application and this is reflected in its widespread global adoption.Therefore, the excessive hesitance of its acceptance by Ethiopia and campaigners that support this stance is unjustifiable either socially, economically, or more importantly, scientifically.

Main Image: Children at a farm in Hawzen, Tigray region. Ethiopia Observer file.

This article is published under aCreative Commons Attribution-NonCommercial 4.0 International licence. Please cite Ethiopia Observer prominently and link clearly to the original article if you republish. If you have any queries, please contact us at ethiopiaobserver@protonmail.com. Check individual images for licensing details.

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Why Ethiopia needs to embrace gene-modification technology - ethiopiaobserver.com

You may not think of plants as needing life-saving medicine, but that's sometimes the case when bugs and disease strike. Now, scientists have developed a super-accurate, highly delicate way of delivering drugs, and right where plants need them.

At the moment, plants can be sprayed with pesticides, which doesn't really penetrate to the roots, or they can be treated with large needles that aren't particularly precise, and tend to cause damage to the plants.

The new method makes use of microneedles or what the researchers are calling 'phytoinjectors', sitting on top of a silk-based biomaterial patch, which are able to hit a plant's circulatory system directly. Pesticides, in contrast, might travel between the root system and the leaves.

(Cao et al., Advanced Science, 2020)

As well as delivering medicine or nutrients to different parts of the plant, the new mechanism could also be used to take samples of a plant, which are then transferred to a lab for analysis, or even to edit DNA (something the team has successfully tried).

"We wanted to solve the technical problem of how you can have a precise access to the plant vasculature," says mechanical engineer Yunteng Caofrom MIT.

"You can think about delivering micronutrients, or you can think about delivering genes, to change the gene expression of the plant or to basically engineer a plant."

The motivation for the project came from the spread of the citrus greening disease across the US and other parts of the world, which threatens to flatten an industry worth $9 billion if a solution isn't found. Olives and bananas are other fruits under particular threat from disease across the world right now.

Previous work looking at the use of microneedles to deliver human vaccines was used as a starting point, with silk kept as the basis of the material holding the microneedles.

Silk is strong, doesn't cause a reaction in plants, and can be made degradable enough to get out of the way once the drugs have been delivered.

However, a lot also had to change compared to microneedles used on humans: plants have far less water available than the human body does, so the design had to be adapted.

The team of scientists was able to boost the silk's hydrophilicity (water-attracting capabilities), and come up with a new material more suited for plants.

"We found that adaptations of a material designed for drug delivery in humans to plants was not straightforward, due to differences not only in tissue vasculature, but also in fluid composition," says biologist Eugene Lim.

Tests of the material and its microneedled payload on tomato and tobacco plants showed that it could be successful as a drug delivery system. Fluorescent molecules were used to track the progress of the injection all the way from the roots to the leaves.

The system should adapt to other plants fairly easily, the researchers say, though scaling it up is going to prove more challenging. The work should prove useful for future projects though, both in delivering life-saving drugs to save plants from disease, and in engineering them to avoid disease in the first place.

"For the future, our research interests will go beyond antibiotic delivery to genetic engineering and point-of-care diagnostics based on metabolite sampling," says environmental engineer Benedetto Marelli.

The research has been published in Advanced Science.

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Scientists Find New Way to Inject Plants With Medicine, And It May Help Save Our Crops - ScienceAlert