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CRISPR Technology Turns 10, Rises to New Challenges

Ever since CRISPR technology arrived, it has been refining its capabilities and tackling increasingly difficult problems—including problems of global…

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CRISPR excites ambition. Just consider a few CRISPR applications: gene drives (showing promise as a way to prevent malaria); ex vivo and in vivo gene therapies (entering clinical trials); and diagnostic tests (gaining momentum now that two assays have secured emergency use authorization for a raging pandemic disease—namely, COVID-19).

All of these applications can be traced back to research that was led by Emmanuelle Charpentier, PhD, and Jennifer Doudna, PhD. This research was introduced in a 2012 Science article that described the repurposing of a natural CRISPR system, an RNA-guided DNA endonuclease, as gene editing tool. Readers of the article may have noticed that its conclusion—that CRISPR “could offer considerable potential for gene targeting and genome editing applications”—was deliberately understated. Essentially, readers were invited to imagine how profound CRISPR applications might become, or how quickly these applications might leave the laboratory and enter the wider world.

Because CRISPR applications promise so many benefits, we are impatient to see them realized. Indeed, we may complain that the development of CRISPR therapies is too slow. Nonetheless, a handful of CRISPR therapies have advanced to the early stages of clinical trials, including therapies for sickle-cell anemia, HIV disease, and acute myeloid leukemia. And last year, a gene edited allogeneic chimeric antigen receptor T-cell therapy secured the FDA’s regenerative medicine advanced therapy (RMAT) designation for the treatment of relapsed or refractory CD19-positive B-cell malignancies.

We are eager to see CRISPR succeed not just in medicine, but in other application areas where humanity faces serious challenges—areas that include crop production, bioenergy, manufacturing, and environmental remediation. To hasten progress in all these areas, scientists are working diligently to add tools to the CRISPR toolbox. A selection of the most interesting new tools are presented in this CRISPR anniversary article.

Programmable gene insertion

Programmable and multiplexed genome integration of large, diverse DNA cargo independent of DNA repair remains an unsolved challenge of genome editing. Current gene integration approaches require double-strand breaks that stimulate DNA damage responses. Furthermore, CRISPR-based methods that bypass double-strand breaks, such as prime editing, are limited to modification or insertion of short sequences.

In late 2021, Jonathan S. Gootenberg, PhD, and Omar O. Abudayyeh, PhD, both alumni of the MIT laboratory led by Feng Zhang, PhD, presented their latest CRISPR system, PASTE (Programmable Addition via Site-specific Targeting Elements). This technology achieves efficient and versatile gene integration at diverse loci by directing insertion with a CRISPR-Cas9 nickase fused to both a reverse transcriptase and a serine integrase. Without generating double-strand breaks, PASTE can integrate sequences as large as ~36 kb with rates of between 10 and 50% at multiple genomic loci in human cell lines, primary cells, and quiescent nondividing primary human cells.

Jonathan S. Gootenberg, PhD

“The PASTE technology enables programmable gene insertion and the ability to put large cargos into the genome anywhere you want,” Gootenberg said. “It’s the final frontier for therapeutics but also cell engineering and basic biology because we can craft the genome any way we want. I have this enormous piece of cargo, and I can drop it in [the genome] where I want.”

One of the best applications of programmable gene insertion is in therapeutics. “There are companies that are using advanced CRISPR approaches that make single-nucleotide or small edits,” Gootenberg remarked. These approaches are fascinating, he noted, but he added that they may not work with genes that harbor many mutations.

“The cystic fibrosis transmembrane conductance regulator gene, for example, has about 1,800 different mutations,” Gootenberg pointed out. “You’re not going to develop 1,800 different drugs for cystic fibrosis. So, instead of taking that approach, you could replace the gene entirely with a healthy one. Then you don’t even need to know what mutation the patient has.”

Cell-type-specific delivery

Omar O. Abudayyeh
Omar O. Abudayyeh, PhD

Arguably the biggest challenge in realizing the full potential of CRISPR, according to not only Gootenberg and Abudayyeh but also Doudna, is improved in vivo delivery. She believes we’ll see it in the next decade. Doudna told GEN, “To reach the point where CRISPR is the standard of care for all the types of diseases we know it can address, we need to be able to target more cell and tissue types precisely.” Doudna said that this is important for developing therapies that are affordable and accessible.

For diseases that require systemic administration of CRISPR-Cas9 systems, cell-type-specific delivery is ideal to avoid delivery-mediated off-target effects. Although viral and nanoparticle delivery systems have shown promise, especially for delivery to the liver, there’s a lot to be done in other cells or tissues, especially to enhance selectivity. Efforts to achieve cell-type-specific gene delivery with nonviral vectors have spanned surface modification by various targeting moieties, such as small-molecule ligands, peptides, and antibodies. One route is to use aptamers, single-stranded oligonucleotides that fold into defined architectures and bind to targets such as proteins.

 

Spotlight Therapeutics' Targeted Active Gene Editor (TAGE) platform illustration
Spotlight Therapeutics develops cell-targeted in vivo CRISPR gene editing biologics by employing its Targeted Active Gene Editor (TAGE) platform. Each TAGE is a CRISPR effector that leverages a synergistic interaction between an antibody (Ab) and a cell-penetrating peptide (CPP) moiety. The Ab facilitates cell targeting, and the CPP moiety facilitates nuclear trafficking. The company’s approach forgoes the use of complex viral, viral-like, and nanoparticle delivery systems.

Spotlight Therapeutics is addressing multiple limitations of the current in vivo delivery systems by developing engineered ribonucleoproteins with its Targeted Active Gene Editing (TAGE) platform. These ribonucleoproteins are created by combining transmembrane trafficking moieties (cell-penetrating peptides) and a cell-targeting moiety (ligand or antibody) with a CRISPR nuclease.

Mary Haak-Frendscho
Mary Haak-Frendscho, PhD
Spotlight

“We took a biologics approach, and our architecture is riffing off the success of antibody conjugates for dragging payloads to selected cells,” said Mary Haak-Frendscho, PhD, president and CEO of Spotlight. “We are using antibodies or antibody derivatives to deliver a nuclease effector (Cas9 or Cas12) to a selected cell type already loaded with a guide.”

These biologics have a short half-life and do not persist in vivo after the desired gene editing event. This reduces the risk of off-target cleavage events, minimizes the potential for antidrug immune responses, and allows greater flexibility in dosing.

Gene silencing/activation

The epigenome, nature’s gatekeeper to gene expression, consists of markers that are added or removed by very elegant and highly conserved mechanisms to determine the identity and function of each cell. For example, these markers do a great job of ensuring that our neurons stay neurons throughout our lifetimes. By targeted modulation of the epigenome, gene expression can be tweaked without ever cutting or breaking the DNA, which avoids some collateral damage that can come from using gene editing.

Catherine Stehman-Breen
Catherine Stehman-Breen, MD
Chroma Medicine

According to Catherine Stehman-Breen, MD, CEO of epigenetic medicines developer Chroma Medicine, genetic regulation via gene editing is like stopping your car by crashing into a light post. “The horn is blaring, the windshield is broken, and the car is stopped,” Stehman-Breen explained. “You would have had a lot less damage if only you had used the brake—the device that’s meant to stop the car. That’s how I think about epigenetics.”

Chroma Medicine is providing a modular, flexible, CRISPR-based platform for developing epigenetic medicines based on the silencing or activation of genes.

Chroma Medicine's programmable epigenetic editors illustration
Chroma Medicine develops programmable epigenetic editors that target genes and control chromatin conformation. These editors may be used to silence or activate single genes. Also, they may be used to target multiple genes simultaneously. Each editor incorporates a DNA binding domain, a histone modification domain, and a DNA methylation effector domain.

The platform couples a DNA binding domain with epigenetic effector domains. The DNA binding domain specifically targets the gene (or genes) to be silenced or activated. The effector domains create specific methylation patterns which control chromatin conformation and govern whether a gene is accessible or inaccessible for transcription. In simple applications, single genes may be targeted. In more complex applications, multiple genes may be targeted at the same time. It is even possible for some genes to be silenced while others are activated.

Stehman-Breen said that the complex multiplexing that Chroma’s platform offers can be used in a host of ways. For example, these tools can be used in cell therapy, where it may not be ideal to do complex multiplexing with gene editing since some of the challenges, such as transpositions, start to become exponentially more difficult. “With epigenetic modulation,” Stehman-Breen remarked, “you can manipulate as many genes as you want without resulting in any cuts or mixing of the DNA.”

Microbiome modulation

A growing trend in the CRISPR world relates to the microbiome. CRISPR is being packaged into phages to affect bacteria in this setting, which is the opposite of how the CRISPR system exists in nature—bacteria use CRISPR to fight off phages. Irony aside, CRISPR technologies have the potential to enable unprecedented control over microbiome populations. For example, one may eliminate drug-resistant bacteria without targeting beneficial bacteria. This kind of control is critical to addressing antibiotic resistance, which is spreading rapidly around the world and seriously impeding efforts to control microbial infections.

Killing selected bacterial populations just one way to exert control over the microbiome. Another way is to genetically modify bacteria so that they express therapeutic proteins and peptides. The second form of control raises the prospect of hijacking bacteria to modulate critical processes such as metabolic and immunological processes.

Christian Grondahl,
Christian Grøndahl, PhD
Snipr Biome

Both microbiome control approaches are being explored at Snipr Biome, a Danish company that has developed a proprietary technology called CRISPR-Guided Vectors. “We can modulate the microbiome by inserting genes that express proteins, antibodies, enzymes, or small hormones to achieve a therapeutic output,” said Christian Grøndahl, PhD, Snipr Biome’s co-founder and CEO. He added that the company’s technology could be used to modulate the microbiome and treat diseases such as type 2 diabetes, obesity, nonalcoholic fatty liver disease, and irritable bowel disorder.

Safety is a big concern when making a chronic and live treatment. “If you introduce a gene,” Grøndahl pointed out, “you also have to be able to control it and shut it off when you have obtained your treatment effect or when you want to lower the output.” To do so, Snipr Biome is using its technology to install “safety switches” that allow inserted genes to be excised—a better alternative to harvesting the microbiome completely.

“Although you want to go in and modulate the microbiome, you don’t want to disturb the pristine diversity of the microbiome,” Grøndahl stated. “Therefore, it’s not a good idea just to give antibiotics to cut off your treatment.”

The next 10 years of CRISPR

In the next 10 years, we will likely see a growing number of CRISPR-based diagnostics and approved medicines. We may even see people treated safely and effectively for genetic diseases we thought would never be curable. It’s possible that there will be so much headway made in the CRISPR space on literal and metaphorical bandages, that people will be able to preemptively alter the health of individuals.

Along these lines, Doudna’s take on the therapeutic use of CRISPR in the next decade isn’t for treatment—it’s for prevention. “There has been a lot of attention on CRISPR’s potential to treat specific diseases, but I also think that we’ll start seeing new applications to prevent disease in the coming years,” Doudna related. “We’re already seeing CRISPR being used as a diagnostic, and we’ve all seen how important fast, accurate diagnostics are to prevent the spread of disease. But we can also edit genes that predispose people to disorders, including diseases of aging.”

With all of the excitement in the healthcare space, it’s easy to overlook all of the potential good that can be done for the future of the planet. While there’s plenty to be excited about regarding the clinical applications of CRISPR, Doudna thinks that the agriculture and climate applications have the potential to have an even more significant impact worldwide.

“We’re starting to see CRISPR-edited agricultural products now,” Doudna noted. “We’ll see many more over the coming years addressing issues like food security, drought and flood tolerance, reducing pesticide and fertilizer use, eliminating agricultural emissions, as well as carbon removal and sequestration.”

For all of the uncertainty that lies ahead, one thing we can all be sure about is that CRISPR will likely have a role in shaping the future of individuals and the planet.

The post CRISPR Technology Turns 10, Rises to New Challenges appeared first on GEN - Genetic Engineering and Biotechnology News.

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FDA’s drug shortages leader wants companies to start reporting increases in demand

It is no secret that drug shortages have been prevalent in 2022. Several major drug products, such as amoxicillin and Adderall, have been in short supply…

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It is no secret that drug shortages have been prevalent in 2022. Several major drug products, such as amoxicillin and Adderall, have been in short supply for several months and have led to members of Congress applying pressure on the FDA and HHS to resolve the situation.

Valerie Jensen

Speaking at a webinar hosted by the Alliance for a Stronger FDA, Valerie Jensen, the associate director of the FDA’s Drug Shortage Staff, noted both the rise in quality-related issues and increased demand for some products. She called on companies to report such demand increases, even though they are not currently required to do so.

During the Covid-19 pandemic, she said, the agency has seen new challenges mainly related to these increases in demand.

“During the pandemic as well, we had competition on manufacturing lines and that’s still occurring due to vaccine production and other Covid products,” Jensen said. “So, the same products are being made on those lines that are making the vaccines and Covid-related products, and then that creates a competition situation.”

Jensen added that an increase in demand for manufacturing commodities due to large-scale vaccine production is also leading to shortages. Items such as glass, filters and vial hoppers are in short supply. And now the increased demand is centered around the increase in drugs to counter respiratory illnesses.

She said the physical number of drug shortages currently sits at 123, which is “a little above normal,” but there have been around 100 shortages at any given time over the past seven years. Some of those can be chalked up to companies not producing the volumes required to meet market demand. She also added that there were 38 new shortages in 2021, but the FDA is still dealing with them this year.

For some temporary solutions, Jensen said that she has been coordinating with international regulatory authorities more often, to find out what is being marketed and to see if they can import a drug in short supply in the US. She is also coordinating experts to try to mitigate the situation, providing the public with widely available information as well as expediting the review of anything that manufacturers need to boost supplies.

However, Jensen said that the increase in the demand for drugs is not something that will be going away anytime soon.

“One thing that we really see going forward are these demand increases, this is something that is fairly new to us. It’s something that we’re looking at closely,” she said. “We would really want companies to inform us if they’re seeing spikes in demand because that’s currently not required.”

While producers do need to let the FDA know of supply disruption, companies do not need to let the FDA know of spikes in demand, and Jensen would like to see this changed. Also, she would like to apply different uses for supply chain data to look for signals or patterns and ultimately predict shortages.

Jensen added that in some cases it is impossible to prevent a shortage, but she stresses that better notification of when companies are seeing a spike in demand can be a key solution:

In those cases, when we can prevent (a shortage), we are using those same tools to prevent it. So, we’re expediting review, we’re looking at potential ways that we can use flexibility to allow a product to be on the market while the company fixes a problem. All of those tools are really the same for prevention and mitigation. But I think that really the key is early notification. The earlier companies let us know about an issue the earlier we can deal with it.

With the uptick in respiratory illnesses and shortages of drugs such as amoxicillin, Jensen noted that it’s a matter of reaching out and monitoring the market to see what manufacturers are contending with. Also, Jensen will look to work with pharmacy associations and other trade groups to see what is occurring at the pharmacy level and then “put all of those pieces together” to try and help end the shortage.

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Scientists reveal encouraging findings in first-in-human clinical trial evaluating HIV vaccine approach

NEW YORK and LA JOLLA, CA—While scientists have struggled in the past to create an effective vaccine against HIV, a novel vaccine design strategy being…

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NEW YORK and LA JOLLA, CA—While scientists have struggled in the past to create an effective vaccine against HIV, a novel vaccine design strategy being pursued by researchers at Scripps Research, IAVI, Fred Hutchinson Cancer Center (Fred Hutch) and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) shows new promise, according to data from a first-in-human clinical trial.

Credit: CHRISTOPHER COTTRELL, CREATED WITH BIORENDER.COM

NEW YORK and LA JOLLA, CA—While scientists have struggled in the past to create an effective vaccine against HIV, a novel vaccine design strategy being pursued by researchers at Scripps Research, IAVI, Fred Hutchinson Cancer Center (Fred Hutch) and the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center (VRC) shows new promise, according to data from a first-in-human clinical trial.

In a paper published in Science on December 2, 2022, the scientists reveal critical new insights into their novel vaccine strategy, which involves a stepwise approach to producing antibodies capable of targeting a wide range of HIV variants. 

“The data we are publishing in Science demonstrates for the first time that one can design a vaccine that elicits made-to-order antibodies in humans. We specified in advance certain molecular properties of the antibodies that we wanted to elicit, and the results of this trial show that our vaccine antigen consistently induced precisely those types of antibodies,” says co-senior author William Schief, PhD, a professor and immunologist at Scripps Research and executive director of vaccine design at IAVI’s Neutralizing Antibody Center, whose laboratory developed the vaccine antigen. “We believe this vaccine design strategy will be essential to make an HIV vaccine and may help the field create vaccines for other difficult pathogens.”

The Phase 1 trial, known as IAVI G001, tested the first stage in a multi-stage HIV vaccine regimen the researchers are developing. The trial results show that the vaccine had a favorable safety profile and induced the targeted response in 97% of people who were vaccinated. Importantly, the Science study also provides a detailed immunological analysis of the vaccine responses.

“HIV represents an area of dire unmet need across the world, which is what makes the findings from our Phase 1 clinical trial so encouraging,” says Mark Feinberg, MD, PhD, president and CEO of IAVI. “Through the close-knit collaboration of many different scientists, disciplines and institutions, we are that much closer to designing an effective vaccine that could help end the HIV pandemic.”  

Priming the Immune System

Broadly neutralizing antibodies (bnAbs) are a rare type of antibody that can fight and protect against many different variants of a virus—including HIV. This is why scientists have tried to develop an HIV vaccine that induces bnAbs, but thus far without success.   

The researchers in the study are using a strategy known as ‘germline targeting’ to eventually produce bnAbs that can protect against HIV. The first step of germline targeting involves stimulating the rare immune cells—known as bnAb-precursor B cells—that can eventually evolve into the cells that produce the bnAbs needed to block the virus. To accomplish this first step, the researchers designed a customized molecule—known as an immunogen—that would “prime” the immune system and elicit responses from these rare bnAb-precursor cells.

The overarching goal of the IAVI G001 trial was to determine if the vaccine had an acceptable safety profile and could induce responses from these bnAb-precursor B cells.

“Through extensive safety and tolerability monitoring during the trial, we showed the vaccine had a favorable safety profile, while still inducing the necessary target cells,” says study author Dagna Laufer, MD, vice president and head of clinical development at IAVI. “This represents a large step forward in developing an HIV vaccine that is both safe and effective.”

To determine if the targeted bnAb-precursor B cells were induced, the researchers carried out a sophisticated analytical process.

“The workflow of multidimensional immunological analyses has taken clinical trial evaluation to the next level,” says co-senior author Adrian B. McDermott, PhD, former chief of the Vaccine Immunology Program at the NIAID VRC. “In evaluating these important immunological factors, we helped show why the vaccine antigen was able to induce the targeted response in 97% of vaccine recipients.” 

IAVI G001 was sponsored by IAVI and took place at two sites: George Washington University (GWU) in Washington, D.C., and Fred Hutch in Seattle, enrolling 48 healthy adult volunteers. Participants received either a placebo or two doses of the vaccine antigen, eOD-GT8 60mer, along with an adjuvant developed by the pharmaceutical company GSK. Julie McElrath, MD, PhD, co-senior author, senior vice president and director of Fred Hutch’s Vaccine and Infectious Disease Division, and David Diemert, MD, professor of medicine at GWU School of Medicine and Health Sciences, were lead investigators at the trial sites.

A Deeper Immunological Dive

The study also carefully examined the properties of the antibodies and B cells induced by the vaccine antigen, in what Schief likens to “looking under the car hood” to understand how the immune system operated in response to the vaccine. One analysis showed that the vaccine antigen first stimulated an average of 30 to 65 different bnAb precursors per person vaccinated, and then caused those cells to multiply. This helped explain why the vaccine induced the desired response in almost all participants.

Other analyses delved into the specific mutations the bnAb-precursor B cells acquired over time and how tightly they bound to the vaccine antigen. These investigations showed that that after each dose of the vaccine, the bnAb-precursor B cells gained affinity and continued along favorable maturation pathways.

One concern for this type of vaccine approach is the notion of “competitors”—in other words, the B cells induced by the vaccine antigen that are not bnAb precursors. The researchers extensively studied the “competitor” responses, and the results were very encouraging. Although the majority of the B cells triggered by vaccination were, in fact, “competitors”, these undesired B cells could not match the binding strength of the desired bnAb precursors and did not seem to impede maturation of the bnAb-precursor responses.

“These findings were very encouraging, as they indicated that immunogen design principles we used could be applied to many different epitopes, whether for HIV or even other pathogens,” adds Schief.

With these promising data in hand spanning both safety and immune responses, the researchers will continue to iterate and design boosting immunogens that could eventually induce the desired bnAbs and provide protection against the virus. These findings also come shortly after two additional studies in Immunity published in September 2022, which helped validate the germline-targeting approach for vaccinating against HIV.

“Working together with IAVI, Scripps Research, the VRC, GWU, additional investigators at Fred Hutch and many others, this trial and additional analyses will help inform design of the remaining stages of a candidate HIV vaccine regimen—while also enabling others in the field to develop vaccine strategies for additional viruses,” says McElrath of Fred Hutch.

IAVI, Scripps Research, NIAID, the Bill & Melinda Gates Foundation and the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) through the United States Agency for International Development (USAID) are partnering with the biotechnology company Moderna to develop and test mRNA delivery of these HIV vaccine antigens. Two Phase I clinical trials are underway that build on IAVI G001, one (IAVI G002) at four sites in the U.S. and another (IAVI G003) at the Center for Family Health Research in Kigali, Rwanda, and The Aurum Institute in Tembisa, South Africa. Both are testing mRNA delivery of the eOD-GT8 60mer that was evaluated as recombinant protein in IAVI G001, and the U.S. trial includes a boost antigen designed by the Schief lab and delivered with Moderna mRNA technology. A third trial (HVTN302), at ten sites in the U.S., is testing mRNA delivery of three different stabilized HIV trimers designed in the Schief laboratory that are candidates for late-stage boosters in multi-stage vaccines aiming to induce bnAbs. Using mRNA technology could significantly accelerate the pace of HIV vaccine development as it allows for faster production of clinical trial material.

This work was supported by the Bill & Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery; the IAVI Neutralizing Antibody Center; NIAID; Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery and Scripps Consortium for HIV/AIDS Vaccine Development; and the Ragon Institute of MGH, MIT, and Harvard. Other collaborating organizations include Duke Human Vaccine Institute, Karolinska Institutet, and La Jolla Institute. 

Research at the IAVI Neutralizing Antibody Center that contributed to the development of the vaccine antigen eOD-GT8 60mer was also made possible by the government of the Netherlands through the Minister of Foreign Trade & Development Cooperation and through the generous support of the American people through PEPFAR through USAID. The contents are the responsibility of IAVI and Scripps Research and do not necessarily reflect the views of PEPFAR, USAID, or the United States government.

About IAVI

IAVI is a nonprofit scientific research organization dedicated to addressing urgent, unmet global health challenges including HIV and tuberculosis. Its mission is to translate scientific discoveries into affordable, globally accessible public health solutions. Read more at iavi.org.

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more at www.scripps.edu.


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Chevron will still be drilling in 2050: CEO Mike Wirth

Chevron Corporation (NYSE: CVX) will most certainly be drilling about thirty years from now, says CEO Mike Wirth – in contrast with President Biden who…

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Chevron Corporation (NYSE: CVX) will most certainly be drilling about thirty years from now, says CEO Mike Wirth – in contrast with President Biden who recently reiterated that the U.S. will pull out of drilling.

Chevron is continuing to invest

The oil and gas behemoth plans on spending $15 billion to $17 billion a year to meet the growing demand. Speaking with folks at CNBC’s “Squawk Box”, the chief executive noted:

We’re growing production because world’s growing in terms of demand. We have to look well into the future and invest to meet that demand. We’re up this year 15% in Permian versus same period last year and continuing to invest.

While that’s well-below what the multinational was spending before the COVID pandemic, the output, CEO Wirth added, remains the same as Chevron is now more capital-efficient.

For the year, Chevron shares are up more than 50% at writing.

CEO Wirth’s view of the future

It is noteworthy here that Chevron refused to cave in the face of pressure in recent years to lower production and that’s contributing to the ability of the U.S. today to help its allies fight the Russia-driven energy crisis.

Moving forward as well, CEO Mike Wirth sees future in a blend of clean energy and hydrocarbons.

Affordable energy is essential for economic prosperity, reliable energy for national security, and environmental protection is essential for a sustainable planet. We have to balance all three. If you over index one, you can create vulnerabilities.

In related oil news, OPEC+ is expected to reveal plans of further cutting production on Sunday.

The post Chevron will still be drilling in 2050: CEO Mike Wirth appeared first on Invezz.

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