CRISPR & Genetic Engineering News and Discussions

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New study indicates how deep learning can improve gene therapies and antiviral drugs
https://phys.org/news/2022-05-deep-gene ... drugs.html
by Helmholtz Association of German Research Centres

The nuclease Cas13b associated with CRISPR defense systems—also known as genetic scissors—has the potential to be used in the future in hereditary diseases to silence adverse genes. In the fight against infections, it is also being researched as an antiviral agent, as Cas13b can target the genome of viruses and render them harmless. Despite these promising features, researchers are looking for nuclease inhibitors that can control or stop such activities. The aim is to increase the safety and efficacy of future therapies and to help prevent off-target effects.

An international team led by the Helmholtz Institute in Würzburg, in cooperation with the University of Freiburg, has now applied deep learning for the first time to find natural nuclease inhibitors. The study, published today in the scientific journal Molecular Cell, identified the first such inhibitor that blocks the activity of Cas13b.

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Streamlining stem cells to treat macular degeneration
https://medicalxpress.com/news/2022-06- ... ation.html
by Ecole Polytechnique Federale de Lausanne

As we age, so do our eyes; most commonly, this involves changes to our vision and new glasses, but there are more severe forms of age-related eye problems. One of these is age-related macular degeneration, which affects the macula—the back part of the eye that gives us sharp vision and the ability to distinguish details. The result is a blurriness in the central part of our visual field.

The macula is part of the eye's retina, which is the light-sensitive tissue mostly composed of the eye's visual cells: cone and rod photoreceptor cells. The retina also contains a layer called the retinal pigment epithelium (RPE), which has several important functions, including light absorption, cleaning up cellular waste, and keeping the other cells of the eye healthy.

The cells of the RPE also nourish and maintain the eye's photoreceptor cells, which is why one of the most promising treatment strategies for age-related macular degeneration is to replace aging, degenerating RPE cells with new ones grown from human embryonic stem cells.

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Researchers develop online portal to show how biases in RNA sequences affect gene expression
https://phys.org/news/2022-06-online-po ... ences.html
by Hillary Smith, University of Kentucky

A recent publication from researchers at the University of Kentucky explains the importance of identifying and understanding how differences between tissues and cells alter gene expression without changing the underlying genetic code.

Introductory biology classes teach that DNA is transcribed into RNA, which is then translated into proteins. However, many cellular processes affect how quickly transcription and translation occur. Gene expression looks at the differences in RNA concentrations within a cell, and it can help scientists know which genes are active within that tissue or cell.

"Changes in gene expression can significantly affect various diseases and disease trajectories," said Justin Miller, Ph.D., assistant professor in the UK College of Medicine's Department of Pathology and Laboratory Medicine.

Miller, who is also affiliated with the Sanders-Brown Center on Aging and Biomedical Informatics, says he and his colleagues previously developed the first algorithm to identify ramp sequences from a single gene sequence. Through their recent work, Miller and fellow UK co-authors Mark Ebbert, Ph.D., and Matthew Hodgman created an online version of that algorithm and showed that ramp sequences change between tissues and cells without changing the RNA sequence.

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New functional protein measuring technology could advance drug discovery research
https://phys.org/news/2022-06-functiona ... -drug.html
by Stony Brook University

A new biomedical research tool that enables scientists to measure hundreds of functional proteins in a single cell could offer new insights into cell machinery. Led by Jun Wang, Associate Professor of Biomedical Engineering at Stony Brook University, this microchip assay—called the single-cell cyclic multiplex in situ tagging (CycMIST) technology—may help to advance fields such as molecular diagnostics and drug discovery. Details about the cyclic microchip assay method are published in Nature Communications.

While newer technologies of single-cell omics (ie, genomics, transcriptomics, etc.) are revolutionizing the study of complex biological and cellular systems and scientists can analyze genome-wide sequences of individual cells, these technologies do not apply to proteins because they are not amplifiable like DNAs. Thus, protein analysis in single cells has not reached large-scale experimentation. Because proteins represent cell functions and biomarkers for cell types and disease diagnosis, further analysis on a single-cell basis is needed.

"The CycMIST assay enables comprehensive evaluation of cellular functions and physiological status by examining 100 times more protein types than conventional immunofluorescence staining, which is a distinctive feature not achievable by any other similar technology," explains Liwei Yang, lead author of the study and a postdoctoral scholar within the Wang research team and Multiplex Biotechnology Laboratory.

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Soft' CRISPR may offer a new fix for genetic defects
https://phys.org/news/2022-07-soft-cris ... fects.html
by University of California - San Diego

Curing debilitating genetic diseases is one of the great challenges of modern medicine. During the past decade, development of CRISPR technologies and advancements in genetics research brought new hope for patients and their families, although the safety of these new methods is still of significant concern.

Publishing July 1 in the journal Science Advances, a team of biologists at the University of California San Diego that includes postdoctoral scholar Sitara Roy, specialist Annabel Guichard and Professor Ethan Bier describes a new, safer approach that may correct genetic defects in the future. Their strategy, which makes use of natural DNA repair machinery, provides a foundation for novel gene therapy strategies with the potential to cure a large spectrum of genetic diseases.

In many cases, those suffering from genetic disorders carry distinct mutations in the two copies of genes inherited from their parents. This means that often, a mutation on one chromosome will have a functional sequence counterpart on the other chromosome. The researchers employed CRISPR genetic editing tools to exploit this fact.

[Time_Traveller]

The first CRISPR gene-editing drug is coming—possibly as soon as next year

Yesterday 7:00 AM

Until recently, CRISPR—the gene-editing technology that won scientists Jennifer Doudna and Emmanuelle Charpentier the 2020 Nobel Prize in chemistry—sounded more like science fiction than medicine; lab-created molecular scissors are used to snip out problematic DNA sections in a patient’s cells to cure them of disease. But soon we could see regulators approve the very first treatment using this gene-editing technology in an effort to combat rare inherited blood disorders that affect millions across the globe.

In a $900 million collaboration, rare disease specialist Vertex and CRISPR Therapeutics developed the therapy, dubbed exa-cel (short for exagamglogene autotemcel). It has already amassed promising evidence that it can help patients with beta thalassemia and sickle cell disease (SCD), both of which are genetic blood diseases that are relatively rare in the U.S. but somewhat more common inherited conditions globally.

Beta thalassemia is characterized by damaged or missing genes that cause the body to produce less hemoglobin (an essential protein that transports oxygen), potentially leading to enlargement of the liver, spleen, or heart, and malformed or brittle bones. It is estimated to afflict 1 in 100,000 people in the world, and regular blood transfusions are necessary to stave off its most serious effects.

While the exact statistics are unknown, SCD is estimated to affect 100,000 people in the U.S. and millions around the world; it is attributed to a defective gene that causes malformed hemoglobin that are stiff, sticky, and sickle-shaped (hence the name) and can thus block healthy blood cells from transporting oxygen around the body.

Exa-cel reportedly slashed the need for blood transfusions or incidence of serious, life-threatening medical events for months to years after patients received the treatment. New and impressive clinical trial results were announced at a major international medical conference in June and bolstered the companies’ prospect of producing the first gene-editing therapy of its kind to reach the broader market and patients.

https://www.msn.com/en-us/health/medica ... ar-AAZ42sA

[weatheriscool]

The first CRISPR gene-editing drug is coming—possibly as soon as next year

Yesterday 7:00 AM

Until recently, CRISPR—the gene-editing technology that won scientists Jennifer Doudna and Emmanuelle Charpentier the 2020 Nobel Prize in chemistry—sounded more like science fiction than medicine; lab-created molecular scissors are used to snip out problematic DNA sections in a patient’s cells to cure them of disease. But soon we could see regulators approve the very first treatment using this gene-editing technology in an effort to combat rare inherited blood disorders that affect millions across the globe.

In a $900 million collaboration, rare disease specialist Vertex and CRISPR Therapeutics developed the therapy, dubbed exa-cel (short for exagamglogene autotemcel). It has already amassed promising evidence that it can help patients with beta thalassemia and sickle cell disease (SCD), both of which are genetic blood diseases that are relatively rare in the U.S. but somewhat more common inherited conditions globally.

Beta thalassemia is characterized by damaged or missing genes that cause the body to produce less hemoglobin (an essential protein that transports oxygen), potentially leading to enlargement of the liver, spleen, or heart, and malformed or brittle bones. It is estimated to afflict 1 in 100,000 people in the world, and regular blood transfusions are necessary to stave off its most serious effects.

While the exact statistics are unknown, SCD is estimated to affect 100,000 people in the U.S. and millions around the world; it is attributed to a defective gene that causes malformed hemoglobin that are stiff, sticky, and sickle-shaped (hence the name) and can thus block healthy blood cells from transporting oxygen around the body.

Exa-cel reportedly slashed the need for blood transfusions or incidence of serious, life-threatening medical events for months to years after patients received the treatment. New and impressive clinical trial results were announced at a major international medical conference in June and bolstered the companies’ prospect of producing the first gene-editing therapy of its kind to reach the broader market and patients.

https://www.msn.com/en-us/health/medica ... ar-AAZ42sA

One big step towards the future of enhanced humans that are 200+ iq's and can live thousands of years without sickness or illness. Faster the better.

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Large Scale Functions of Human Genes Have Been Determined and Mapped

https://www.nextbigfuture.com/2022/07/l ... apped.html
July 3, 2022 by Brian Wang

You may have thought the human genome was “solved” decades ago when it was first declared fully sequenced in 2003. However, the “complete” sequencing was incomplete with many gaps and errors and we did not know what almost all of the genes did. 8% of the genome was completely sequenced, due to highly repetitive DNA segments that are difficult to match with the rest of the genome

Now a first truly complete sequencing of the human genome was achieved. The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes. Of the protein-coding genes, the T2T team found about 2,000 new ones, most of them disabled, but 115 of which may still be expressed. They also found about 2 million additional variants in the human genome, 622 of which occur in medically relevant genes.

Large Scale Gene function Exploration

Seperately, new techniques have been applied to determine the functions of the genes on a genome scale.

The Perturb-seq method uses CRISPR-Cas9 genome editing to create genetic changes into cells, and then uses single-cell RNA sequencing to capture information about the RNAs that are expressed resulting from a given genetic change. Because RNAs control all aspects of how cells behave, this method can help decode the many cellular effects of genetic changes.

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New screening technique could accelerate and improve mRNA therapies

by Jerry Grillo, Georgia Institute of Technology
https://phys.org/news/2022-07-screening ... apies.html

Therapeutics based on messenger RNA, or mRNA, can potentially treat a wide range of maladies, including cancer, genetic diseases, and as the world has learned in recent years, deadly viruses.

To work, these drugs must be delivered directly to target cells in nanoscale bubbles of fat called lipid nanoparticles, or LNPs—mRNA isn't much good if doesn't reach the right cell type.

A team of researchers at the Georgia Institute of Technology and Emory University's School of Medicine has taken another step toward improving development of these custom-made delivery vehicles, reporting their work June 30 in Nature Nanotechnology. Curtis Dobrowolski and Kalina Paunovska, trainees in the lab of James Dahlman, have developed a system to make pre-clinical nanoparticle studies more predictive. Their discoveries already are influencing the direction of research in this growing, competitive field.

"I'm very excited about this study and anticipate shifting most of our future projects to this methodology," said Dahlman, associate professor and McCamish Foundation Early Career Professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory.

[Xyls]

Verve Therapeutics begins human tests of first ‘base editor,’ aiming at heart disease

https://www.statnews.com/2022/07/12/ver ... se-editor/

Somewhere in New Zealand, the first patient ever has been dosed with a kind of gene-editing treatment known as a base editor, a newer way of utilizing CRISPR for gene editing. The company studying the treatment, Verve Therapeutics, announced the news Tuesday.

The treatment is aimed at a relatively common form of high cholesterol that affects millions of people, a very different population than those normally treated with gene therapies. Eventually, Verve hopes that the treatment might be offered to people who have recently suffered heart attacks, or for other more common diseases.

[Vakanai]

Verve Therapeutics begins human tests of first ‘base editor,’ aiming at heart disease

https://www.statnews.com/2022/07/12/ver ... se-editor/

Somewhere in New Zealand, the first patient ever has been dosed with a kind of gene-editing treatment known as a base editor, a newer way of utilizing CRISPR for gene editing. The company studying the treatment, Verve Therapeutics, announced the news Tuesday.

The treatment is aimed at a relatively common form of high cholesterol that affects millions of people, a very different population than those normally treated with gene therapies. Eventually, Verve hopes that the treatment might be offered to people who have recently suffered heart attacks, or for other more common diseases.

Or you know, maybe offer it to people at risk of heart attack before they have a freaking heart attack?

[weatheriscool]

New DNA repair-kit successfully fixes hereditary disease in patient-derived cells
https://medicalxpress.com/news/2022-07- ... sease.html
by University of Bristol

Genetic mutations which cause a debilitating hereditary kidney disease affecting children and young adults have been fixed in patient-derived kidney cells using a potentially game-changing DNA repair-kit. The advance, developed by University of Bristol scientists, is published in Nucleic Acids Research.

In this new study, the international team describe how they created a DNA repair vehicle to genetically fix faulty podocin, a common genetic cause of inheritable Steroid Resistant Nephrotic Syndrome (SRNS).

Podocin is a protein normally located on the surface of specialized kidney cells and essential for kidney function. Faulty podocin, however, remains stuck inside the cell and never makes it to the surface, terminally damaging the podocytes. Since the disease cannot be cured with medications, gene therapy which repairs the genetic mutations causing the faulty podocin offers hope for patients.

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Researchers add second copy of gene to give rice a 40% yield boost

by Bob Yirka , Phys.org
https://phys.org/news/2022-08-gene-rice ... boost.html

A team of researchers affiliated with several institutions in China, working with a colleague from Germany, has boosted the yield of rice by 40% by giving test plants a second copy of a certain gene. In their paper published in the journal Science, the group describes their work in improving rice yields to meet growing food demands in light of a continuing rise in global population. Steven Kelly with the University of Oxford, has published a Perspectives piece in the same journal issue outlining the work done by the team in China.

As the world's population continues to grow, scientists around the world are looking for ways to get more food out of the land available for use in growing crops. In this new effort, the researchers looked at ways to improve rice yields by genetically altering DNA to coax individual plants to produce more grains of rice.

[caltrek]

CRISPR-based Technology Targets Global Crop Pest
August 18, 2022

Introduction:

(EurekAlert) Applying new CRISPR-based technology to a broad agricultural need, researchers at the University of California San Diego have set their aims on a worldwide pest known to decimate valuable food crops.

Nikolay Kandul, Omar Akbari and their colleagues first demonstrated the precision-guided sterile insect technique, or pgSIT, in Drosophila melanogaster, the common fruit fly, in 2019. The technology, later adapted to mosquitoes, uses programmable CRISPR techniques to edit key genes that control sex determination and fertility. Under the new system, pgSIT-developed insect eggs are deployed into a targeted population and only sterile males hatch, resulting in a fertility dead end for that species.

Kandul, Akbari and their colleagues have now adapted the technology for use in Drosophila suzukii , an invasive fruit fly (also known as the spotted-wing drosophila) responsible for millions of dollars in crop damage. The advancement is described in the journal GEN Biotechnology.

“It’s a safe, evolutionary stable system,” said Akbari, a professor in the School of Biological Sciences’ Department of Cell and Developmental Biology. “Also, the system does not lead to uncontrolled spread nor does it persist in the environment—both important safety features that will help it gain approvals for use.”

D. suzukii flies have invaded many parts of the world and caused widespread agricultural and economic damage to several crops, including apples, cherries, raspberries, blueberries, strawberries, peaches, grapes, olives and tomatoes.

Read more here: https://www.eurekalert.org/news-releases/961913

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A step toward the creation of materials controlled by artificial genes
https://phys.org/news/2022-08-creation- ... genes.html
by Samuel Schaffter and Gina Wadas, Johns Hopkins University

Our bodies' genes work together to regulate how our cells behave. For example, if you skin your knee, your genes use a chemical messaging system to direct an army of cells to heal the abrasion. If scientists could create artificial genes that could carry out the same functions but operate inside materials rather than organisms, a wide variety of new diagnostic, self-healing materials would be possible.

A team led by Johns Hopkins engineer Rebecca Schulman is laying the foundation for that work by engineering synthetic chemical systems that can emulate the complex behaviors of natural gene networks. Their work recently appeared in Nature Chemistry.

"Cells use genes to decide how to move, grow, and act. The ability to make simple 'genes' that could make decisions on their own could lead to better diagnostics or therapeutics, or even provide ways to build new types of soft material robots that are controlled by chemistry instead of electronics," said Schulman, who is an associate professor of chemical and biomolecular engineering and associate researcher at the Whiting School of Engineering's Institute for NanoBioTechnology.

The human body comprises about 25,000 genes, and the chemical interactions that these genes use to regulate cells have many steps and moving parts. Researchers have learned that they don't need to meticulously recreate every one of these natural biological steps to create synthetic gene analogs capable of carrying out the same functions. To improve and better predict the behavior of gene analogs, Schulman and her team created a molecular tool kit which includes genelets (very small genes whose functions can vary, depending on instructions), and simplified mathematical models that predict how the genelets will behave.

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Microscopy reveals mechanism behind new CRISPR tool
https://phys.org/news/2022-08-microscop ... -tool.html
by Cornell University

New research from Cornell offers insights into a line of CRISPR systems, which could lead to promising antiviral and tissue engineering tools in animal and plants.

The research by Ailong Ke, the Robert J. Appel Professor of molecular biology and genetics in the College of Arts and Sciences, and Stan J.J. Brouns at Delft University of Technology in the Netherlands, focuses on a newly discovered CRISPR RNA-guided Caspase system, otherwise known as Craspase.

CRISPR-Cas systems are RNA-guided nucleases in bacteria that cleave viral DNA or RNA targets in precise locations to enable powerful genome editing applications. Caspases are a family of proteases that control programmed cell death in animals, including humans. A recent finding that caspase-like proteins could associate with CRISPR-Cas electrified the scientific community. Such CRISPR-guided caspases were given a new name, Craspase.

"On one hand, this association was totally unexpected and points to novel modes of antiviral action in bacteria," Ke said. "On the other hand, we could use a system like this to develop many biotech and therapeutic applications, if we understand all the gizmos inside this machinery."

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A cellular engineering breakthrough: High-yield CRISPR without viral vectors
https://phys.org/news/2022-08-cellular- ... viral.html
by Sarah Williams, Gladstone Institutes

A new variation of the CRISPR-Cas9 gene editing system makes it easier to re-engineer massive quantities of cells for therapeutic applications. The approach, developed at Gladstone Institutes and UC San Francisco (UCSF), lets scientists introduce especially long DNA sequences to precise locations in the genomes of cells at remarkably high efficiencies without the viral delivery systems that have traditionally been used to carry DNA into cells.

"One of our goals for many years has been to put lengthy DNA instructions into a targeted site in the genome in a way that doesn't depend on viral vectors," says Alex Marson, MD, Ph.D., director of the Gladstone-UCSF Institute of Genomic Immunology and senior author of the new study. "This is a huge step toward the next generation of safe and effective cell therapies."

In the new paper published in the journal Nature Biotechnology, Marson and his colleagues not only describe the technology but show how it can be used to generate CAR-T cells with the potential to fight multiple myeloma, a blood cancer, as well as to rewrite gene sequences where mutations can lead to rare inherited immune diseases.

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Stem cell-gene therapy shows promise in ALS safety trial

by Cedars-Sinai Medical Center
https://medicalxpress.com/news/2022-09- ... html[quote]

Cedars-Sinai investigators have developed an investigational therapy using support cells and a protective protein that can be delivered past the blood-brain barrier. This combined stem cell and gene therapy can potentially protect diseased motor neurons in the spinal cord of patients with amyotrophic lateral sclerosis, a fatal neurological disorder known as ALS or Lou Gehrig's disease.

In the first trial of its kind, the Cedars-Sinai team showed that delivery of this combined treatment is safe in humans. The findings were reported today in the peer-reviewed journal Nature Medicine.

"Using stem cells is a powerful way to deliver important proteins to the brain or spinal cord that can't otherwise get through the blood-brain barrier," said senior and corresponding author Clive Svendsen, Ph.D., professor of Biomedical Sciences and Medicine and executive director of the Cedars-Sinai Board of Governors Regenerative Medicine Institute. "We were able to show that the engineered stem cell product can be safely transplanted in the human spinal cord. And after a one-time treatment, these cells can survive and produce an important protein for over three years that is known to protect motor neurons that die in ALS."

Aimed at preserving leg function in patients with ALS, the engineered cells are potentially a powerful therapeutic option for this disease that causes progressive muscle paralysis, robbing people of their ability to move, speak and breathe. [/quote]

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Researchers develop gene therapy for rare ciliopathy
https://medicalxpress.com/news/2022-09- ... pathy.html
by National Eye Institute

Researchers from the National Eye Institute (NEI) have developed a gene therapy that rescues cilia defects in retinal cells affected by a type of Leber congenital amaurosis (LCA), a disease that causes blindness in early childhood. Using patient-derived retina organoids (also known as retinas-in-a-dish), the researchers discovered that a type of LCA caused by mutations in the NPHP5 (also called IQCB1) gene leads to severe defects in the primary cilium, a structure found in nearly all cells of the body. The findings not only shed light on the function of NPHP5 protein in the primary cilium, but also led to a potential treatment for this blinding condition. NEI is part of the National Institutes of Health.

"It's so sad to see little kids going blind from early onset LCA. NPHP5 deficiency causes early blindness in its milder form, and in more severe forms, many patients also exhibit kidney disease along with retinal degeneration," said the study's lead investigator, Anand Swaroop, Ph.D., senior investigator at the NEI Neurobiology Neurodegeneration and Repair Laboratory. "We've designed a gene therapy approach that could help prevent blindness in children with this disease and one that, with additional research, could perhaps even help treat other effects of the disease."

LCA is a rare genetic disease that leads to degeneration of the light-sensing retina at the back of the eye. Defects in at least 25 different genes can cause LCA. While there is an available gene therapy treatment for one form of LCA, all other forms of the disease have no treatment. The type of LCA caused by mutations in NPHP5 is relatively rare. It causes blindness in all cases, and in many cases it can also lead to failure of the kidneys, a condition called Senior-Løken Syndrome.

[weatheriscool]

New approach more than doubles stem cell editing efficiency, researchers report
https://phys.org/news/2022-09-approach- ... iency.html
by Mary Fetzer, Pennsylvania State University

A Penn State-led team of interdisciplinary researchers has developed techniques to improve the efficiency of CRISPR-Cas9, the genome editing technique that earned the Nobel Prize in 2020. While CRISPR-Cas9 is faster, less expensive and more accurate than other gene-editing methods, according to project leader Xiaojun "Lance" Lian, associate professor of biomedical engineering and biology at Penn State, the technology has limitations—especially in applications to improve human health.

The researchers developed a more efficient and accessible process to apply CRISPR-Cas9 systems in human pluripotent stem cells (hPSCs), derived from federally approved stem cell lines, which Lian said could greatly advance diagnostics and treatments for genetic disorders. The approach was published Sept. 7 in Cell Reports Methods.

CRISPR-Cas9, which stands for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, gives scientists the ability to target precise locations of genetic code to change DNA, providing opportunities to create new diagnostic tools and potentially correct mutations to treat genetic causes of disease.

"The human genome is enormous, and CRISPR-Cas9 makes it possible for scientists to find and target a mutated gene for the purpose of studying it," Lian said.

CRISPR uses a disc of genetic material, known as plasmid DNA, to deliver guided ribonucleic acid (RNA) that positions the Cas9 enzyme at the precise location of the target gene. When the DNA is located, Cas9 binds to it and cuts it out, allowing other DNA to repair the cut. Researchers can then see how the removal changes the gene's expression. But there are delivery and editing efficiency problems with current DNA-based CRISPR methods, according to Lian.