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At MIT, New DNA Microscopy Maps Cells and Their Genetic Sequences Using Chemicals Rather than Light

Genetic data captured by this new technology could lead to a new understanding of how different types of cells exchange information and would be a boon to anatomic pathology research worldwide

What if it were possible to map the interior of cells and view their genetic sequences using chemicals instead of light? Might that spark an entirely new way of studying human physiology? That’s what researchers at the Massachusetts Institute of Technology (MIT) believe. They have developed a new approach to visualizing cells and tissues that could enable the development of entirely new anatomic pathology tests that target a broad range of cancers and diseases.

Scientists at MIT’s Broad Institute and McGovern Institute for Brain Research developed this new technique, which they call DNA Microscopy. They published their findings in Cell, titled, “DNA Microscopy: Optics-free Spatio-genetic Imaging by a Stand-Alone Chemical Reaction.”

Joshua Weinstein, PhD, a postdoctoral associate at the Broad Institute and first author of the study, said in a news release that DNA microscopy “is an entirely new way of visualizing cells that captures both spatial and genetic information simultaneously from a single specimen. It will allow us to see how genetically unique cells—those comprising the immune system, cancer, or the gut for instance—interact with one another and give rise to complex multicellular life.”

The news release goes on to state that the new technology “shows how biomolecules such as DNA and RNA are organized in cells and tissues, revealing spatial and molecular information that is not easily accessible through other microscopy methods. DNA microscopy also does not require specialized equipment, enabling large numbers of samples to be processed simultaneously.”

The images above, taken from the MIT study, compares optical imaging of a cell population (left) with an inferred visualization of the same cell population based on the information provided by DNA microscopy (right). Scale bar = 100 μm (100 micrometers). This technology has the potential to be useful for anatomic pathologists at some future date. (Photo and caption copyrights: Joshua Weinstein, PhD, et al/Cell.)

New Way to Visualize Cells

The MIT researchers saw an opportunity for DNA microscopy to find genomic-level cell information. They claim that DNA microscopy images cells from the inside and enables the capture of more data than with traditional light microscopy. Their new technique is a chemical-encoded approach to mapping cells that derives critical genetic insights from the organization of the DNA and RNA in cells and tissue.

And that type of genetic information could lead to new precision medicine treatments for chronic disease. New Atlas notes that “ Speeding the development of immunotherapy treatments by identifying the immune cells best suited to target a particular cancer cell is but one of the many potential application for DNA microscopy.”

In their published study, the scientists note that “Despite enormous progress in molecular profiling of cellular constituents, spatially mapping [cells] remains a disjointed and specialized machinery-intensive process, relying on either light microscopy or direct physical registration. Here, we demonstrate DNA microscopy, a distinct imaging modality for scalable, optics-free mapping of relative biomolecule positions.”

How DNA Microscopy Works

The New York Times (NYT) notes that the advantage of DNA microscopy is “that it combines spatial details with scientists’ growing interest in—and ability to measure—precise genomic sequences, much as Google Street View integrates restaurant names and reviews into outlines of city blocks.”

And Singularity Hub notes that “ DNA microscopy, uses only a pipette and some liquid reagents. Rather than monitoring photons, here the team relies on ‘bar codes’ that chemically tag onto biomolecules. Like cell phone towers, the tags amplify, broadcasting their signals outward. An algorithm can then piece together the captured location data and transform those GPS-like digits into rainbow-colored photos. The results are absolutely breathtaking. Cells shine like stars in a nebula, each pseudo-colored according to their genomic profiles.”

“We’ve used DNA in a way that’s mathematically similar to photons in light microscopy,” Weinstein said in the Broad Institute news release. “This allows us to visualize biology as cells see it and not as the human eye does.”

In their study, researchers used DNA microscopy to tag RNA molecules and map locations of individual human cancer cells. Their method is “surprisingly simple” New Atlas reported. Here’s how it’s done, according to the MIT news release:

  • Small synthetic DNA tags (dubbed “barcodes” by the MIT team) are added to biological samples;
  • The “tags” latch onto molecules of genetic material in the cells;
  • The tags are then replicated through a chemical reaction;
  • The tags combine and create more unique DNA labels;
  •  The scientists use a DNA sequencer to decode and reconstruct the biomolecules;
  • A computer algorithm decodes the data and converts it to images displaying the biomolecules’ positions within the cells.
The visualization above was created from data gathered by DNA microscopy, which peers inside individual cells. It demonstrates how DNA microscopy enables scientists to identify different cells (colored dots) within a sample—with no prior knowledge of what the sample looks like. (Photo and caption copyright: Joshua Weinstein, PhD, et al./Cell.)

“The first time I saw a DNA microscopy image, it blew me away,” said Aviv Regev, PhD, a biologist at the Broad Institute, a Howard Hughes Medical Institute (HHMI) Investigator, and co-author of the MIT study, in an HHMI news release. “It’s an entirely new category of microscopy. It’s not just a technique; it’s a way of doing things that we haven’t ever considered doing before.”

Precision Medicine Potential

“Every cell has a unique make-up of DNA letters or genotype. By capturing information directly from the molecules being studied, DNA microscopy opens up a new way of connecting genotype to phenotype,” said Feng Zhang, PhD, MIT Neuroscience Professor,

Core Institute Member of the Broad Institute, and Investigator at the McGovern Institute for Brain Research at MIT, in the HHMI news release.

In other words, DNA microscopy could someday have applications in precision medicine. The MIT researchers, according to Stat, plan to expand the technology further to include immune cells that target cancer.

The Broad Institute has applied for a patent on DNA microscopy. Clinical laboratory and anatomic pathology group leaders seeking novel resources for diagnosis and treatment of cancer may want to follow the MIT scientists’ progress.    

—Donna Marie Pocius

Related Information:

A Chemical Approach to Imaging Cells from the Inside

DNA Microscope Sees “Through the Eyes of the Cell”

DNA Microscopy Offers Entirely New Way to Image Cells

DNA Microscopy: Optics-free Spatio-Genetic Imaging by a Stand-Alone Chemical Reaction

This New Radical DNA Microscope Reimagines the Cellular World

DNA Microscopy Offers a New Way to Image Molecules

DNA Microscope Shows Cells Genetic Material

MIT Engineers Develop Physiome-on-a-Chip Device That Tests Multiple Human Organs for Drug Effects; Could it Become a New Clinical Laboratory Test for Complex Multi-Analytes?

“On-a-chip” devices continue to advance and medical laboratories will be natural repositories for patient data as the technology continues to improve

Dark Daily has predicted that the future of clinical laboratory testing will include highly complex multi-analyte test panels. The biomarkers, however, could number in the hundreds or thousands. So, it’s interesting to see new research by a Massachusetts Institute of Technology (MIT) team currently developing a multi-biomarker organ test device for clinical purposes.

Motivated by the costly failure of animal testing efforts to develop drug safety and efficacy in humans, the MIT research engineers created a microfluidic platform technology they dubbed “physiome-on-a-chip,” or more colloquially, “body-on-a-chip.” Their goal is to identify drug reaction in different cell groups within the body (in vivo).

They acknowledged contributions of in vitro microphysiological systems (MPSs), AKA “organ-on-a-chip” (OOC) systems. They note, however, in their paper published in Scientific Reports, that more complex systems that interconnect and receive data from multiple MPSs are needed due to increasing limitations arising from drugs’ “lack of efficacy” rather than toxicity.

“Here we describe the development and implementation of multi-MPS platforms, AKA physiome-on-a-chip, supporting four-way, seven-way, and 10-way MPS interactions for several weeks,” the MIT engineers wrote.

Though MIT’s new technology needs further research and development time, as well as clinical trials, this type of chip design and its ability to scale is a positive development and progress toward Dark Daily’s prediction. Once finalized, it could be adopted in medical laboratories for many types of diagnostic testing purposes.

Researchers Motivated to Improve Drug Efficacy

According to an MIT news release, “MIT engineers have developed new technology that could be used to evaluate new drugs and detect possible side effects before the drugs are tested in humans. Using a microfluidic platform that connects engineered tissues from up to 10 organs, the researchers can accurately replicate human organ interactions for weeks at a time, allowing them to measure the effects of drugs on different parts of the body.”

The “body-on-a-chip” technology, MIT says, is aimed at determining how drugs may affect one organ while also having side effects on others.

“Some of these effects are really hard to predict from animal models because the situations that lead to them are idiosyncratic. With our chip, you can distribute a drug and then look for the effects on other tissues and measure the exposure and how it is metabolized,” said Linda Griffith, PhD, Professor of Teaching Innovation at MIT’s School of Engineering, and a senior author of the study, in the news release.

According to MIT, factors affecting the effectiveness of pharmaceuticals may include:

  • Genetics;
  • Environment;
  • Personal lifestyles; and,
  • Interactions with other drugs.

TechCrunch called the study “unprecedented,” pointing to the platform’s connection of so many tissues and the technology’s ability to keep them stable for weeks.

“An advantage of our platform is that we can scale it up or down and accommodate a lot of different configurations,” Linda Griffith, PhD, MIT Professor, MIT School of Engineering, told Science Daily. “I think the field is going to go through a transition where we start to get more information out of a three-organ or four-organ system, and it will start to become cost-competitive because the information you’re getting is so much more valuable.” (Photo copyright: MacArthur Foundation.)

How “Body-on-a-Chip” Works

“Body-on-a-chip” is about the size of a tablet computer and links 10 organ types, including: liver, lung, gut, endometrium, brain, heart, pancreas, kidney, skin, and skeletal muscle.

Using microfluidic platform technology, the researchers placed one- to two-million cells from human tissue samples into the device and then pushed fluid through the chip to resemble blood flow, the Daily Mail reported, adding that MIT’s MPS platform design features:

  • Compartments made from a plastic block;
  • Passages for fluid to move (as a circulatory system does) between the compartments;
  • A water reservoir to limit fluid evaporation; and,
  • Ability to monitor flow of molecular exchanges and drug distribution.

Essentially, using the MIT device, a drug can be introduced to one organ, processed normally, and then passed to other organs for processing and use in other ways, TechCrunch summarized.

The physiome-on-a-chip system (above schematic) comprises bioengineered devices that nurture many interconnected 3D MPSs representing specified functional behaviors of each organ of interest, designed to capture essential features of in vivo physiology based on quantitative systems models tailored for individual applications such as drug fate or disease modeling. This technology could eventually be utilized for clinical laboratory and anatomic pathology testing. (Image and caption copyright: Victor O. Leshyk/Scientific Reports.)

Drug Delivery, Effects on Multiple Tissues Noted in MIT Study

The MIT researcher engineers reported these findings and accomplishments:

  • Delivering a drug to the gastrointestinal tissue;
  • Replicating digesting a drug;
  • Observing as a drug was transported to other tissues and metabolized;
  • Measuring a drug’s path; and,
  • Noting effects of a drug on different tissues and how drugs break down.

“The huge potential of MPS technology is revealed by connecting multiple organ chips in an integrated system for in vitro pharmacology. This study beautifully illustrates that multi-MPS ‘physiome-on-a-chip’ approaches, which combine the genetic background of human cells with physiologically relevant tissue-to-media volumes, allow accurate prediction of drug pharmacokinetics and drug absorption, distribution, metabolism, and excretion,” said Kevin Healy, PhD, Professor of Bioengineering and Materials Science and Engineering, at University of California Berkeley in the MIT news release. Healy was not involved in the research.

Unique Device Design

In addition to making it possible to study so many different tissue types, the device design, according to MIT, is unique for these reasons:

  • Its open microfluidic system, rather than a closed system, means the lid can be removed to manipulate tissue samples;
  • Instead of external pumps common in closed systems, the MIT team used “on-board pumps” to control flow of liquid between the organs; and,
  • The pumps used enabled larger engineered tissues, such as those from tumors in an organ, to be assessed.

The MIT engineers next plan to focus on specific organs—including the brain, liver, and gastrointestinal tissue—to model Parkinson’s disease, Digital Trends reported.

As healthcare providers and medical laboratories adopt precision medicine, MIT’s contributions are both timely and important. The ability to accommodate many different configurations in one platform is impressive, and something Dark Daily has been anticipating.

—Donna Marie Pocius

Related Information:

A “Body-on-a-Chip” Strings Together 10 Model Human Organs

“Body-on-a-Chip” Could Improve Drug Evaluation

MIT Builds “Body-on-a-Chip” Device That Can Store up to 10 Artificial Organs at Once

Interconnected Microphysiological Systems for Quantitative Biology and Pharmacology Studies

MIT Gadget Puts Multiple Artificial Organs into a Paperback-Sized Connected System

Drug Testing Could Get a Boost from MIT’s “Body-on-a-Chip”

Researchers at Several Top Universities Unveil CRISPR-Based Diagnostics That Show Great Promise for Clinical Laboratories

Three innovative technologies utilizing CRISPR-Cas13, Cas12a, and Cas9 demonstrate how CRISPR might be used for more than gene editing, while highlighting potential to develop new diagnostics for both the medical laboratory and point-of-care (POC) testing markets

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is in the news again! The remarkable genetic-editing technology is at the core of several important developments in clinical laboratory and anatomic pathology diagnostics, which Dark Daily has covered in detail for years.

Now, scientists at three universities are investigating ways to expand CRISPR’s use. They are using CRISPR to develop new diagnostic tests, or to enhance the sensitivity of existing DNA tests.

One such advancement improves the sensitivity of SHERLOCK (Specific High Sensitivity Reporter unLOCKing), a CRISPR-based diagnostic tool developed by a team at MIT. The new development harnesses the DNA slicing traits of CRISPR to adapt it as a multifunctional tool capable of acting as a biosensor. This has resulted in a paper-strip test, much like a pregnancy test, that can that can “display test results for a single genetic signature,” according to MIT News.

Such a medical laboratory test would be highly useful during pandemics and in rural environments that lack critical resources, such as electricity and clean water.

One Hundred Times More Sensitive Medical Laboratory Tests!

Co-lead authors Jonathan Gootenberg, PhD Candidate, Harvard University and Broad Institute; and Omar Abudayyeh, PhD and MD student, MIT, published their findings in Science. They used CRISPR Cas13 and Cas12a to chop up RNA in a sample and RNA-guided DNA binding to target genetic sequences. Presence of targeted sequences is then indicated using a paper-based testing strip like those used in consumer pregnancy tests.

MIT News highlighted the high specificity and ease-of-use of their system in detecting Zika and Dengue viruses simultaneously. However, researchers stated that the system can target any genetic sequence. “With the original SHERLOCK, we were detecting a single molecule in a microliter, but now we can achieve 100-fold greater sensitivity … That’s especially important for applications like detecting cell-free tumor DNA in blood samples, where the concentration of your target might be extremely low,” noted Abudayyeh.

Feng-Zhang-Broad-Institute-500w@96ppi

“The [CRISPR] technology demonstrates potential for many healthcare applications, including diagnosing infections in patients and detecting mutations that confer drug resistance or cause cancer,” stated senior author Feng Zhang, PhD. Zhang, shown above in the MIT lab named after him, is a Core Institute Member of the Broad Institute, Associate Professor in the departments of Brain and Cognitive Sciences and Biological Engineering at MIT, and a pioneer in the development of CRISPR gene-editing tools. (Photo copyright: MIT.)

Creating a Cellular “Black Box” using CRISPR

Another unique use of CRISPR technology involved researchers David Liu, PhD, and Weixin Tang, PhD, of Harvard University and Howard Hughes Medical Institute (HHMI). Working in the Feng Zhang laboratory at the Broad Institute, they developed a sort of “data recorder” that records events as CRISPR-Cas9 is used to remove portions of a cell’s DNA.

They published the results of their development of CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems, in Science. The story was also covered by STAT.

“The order of stimuli can be recorded through an overlapping guide RNA design and memories can be erased and re-recorded over multiple cycles,” the researchers noted. “CAMERA systems serve as ‘cell data recorders’ that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.”

This creates a system much like the “black box” recorders in aircraft. However, using Cas9, data is recorded at the cellular level. “There are a lot of questions in cell biology where you’d like to know a cell’s history,” Liu told STAT.

While researchers acknowledge that any medical applications are in the far future, the technology holds the potential to capture and replay activity on the cellular level—a potentially powerful tool for oncologists, pathologists, and other medical specialists.

Using CRISPR to Detect Viruses and Infectious Diseases

Another recently developed technology—DNA Endonuclease Targeted CRISPR Trans Reporter (DETECTR)—shows even greater promise for utility to anatomic pathology groups and clinical laboratories.

Also recently debuted in Science, the DETECTR system is a product of Jennifer Doudna, PhD, and a team of researchers at the University of California Berkeley and HHMI. It uses CRISPR-Cas12a’s indiscriminate single-stranded DNA cleaving as a biosensor to detect different human papillomaviruses (HPVs). Once detected, it signals to indicate the presence of HPV in human cells.

Despite the current focus on HPVs, the researchers told Gizmodo they believe the same methods could identify other viral or bacterial infections, detect cancer biomarkers, and uncover chromosomal abnormalities.

Future Impact on Clinical Laboratories of CRISPR-based Diagnostics

Each of these new methods highlights the abilities of CRISPR both as a data generation tool and a biosensor. While still in the research phases, they offer yet another possibility of improving efficiency, targeting specific diseases and pathogens, and creating new assays and diagnostics to expand medical laboratory testing menus and power the precision medicine treatments of the future.

As CRISPR-based diagnostics mature, medical laboratory directors might find that new capabilities and assays featuring these technologies offer new avenues for remaining competitive and maintaining margins.

However, as SHERLOCK demonstrates, it also highlights the push for tests that produce results with high-specificity, but which do not require specialized medical laboratory training and expensive hardware to read. Similar approaches could power the next generation of POC tests, which certainly would affect the volume, and therefore the revenue, of independent clinical laboratories and hospital/health system core laboratories.

—Jon Stone

 

Related Information:

Multiplexed and Portable Nucleic Acid Detection Platform with Cas13, Cas12a, and Csm6

Rewritable Multi-Event Analog Recording in Bacterial and Mammalian Cells

CRISPR-Cas12a Target Binding Unleashes Indiscriminate Single-Stranded DNase Activity

Researchers Advance CRISPR-Based Tool for Diagnosing Disease

CRISPR Isn’t Just for Gene Editing Anymore

CRISPR’s Pioneers Find a Way to Use It as a Glowing Virus Detector

With New CRISPR Inventions, Its Pioneers Say, You Ain’t Seen Nothin’ Yet

New CRISPR Tools Can Detect Infections Like HPV, Dengue, and Zika

Breakthrough DNA Editing Tool May Help Pathologists Develop New Diagnostic Approaches to Identify and Treat the Underlying Causes of Diseases at the Genetic Level

CRISPR-Related Tool Set to Fundamentally Change Clinical Laboratory Diagnostics, Especially in Rural and Remote Locations

Harvard Researchers Demonstrate a New Method to Deliver Gene-editing Proteins into Cells: Possibly Creating a New Diagnostic Opportunity for Pathologists

Sales of Direct-to-Consumer Clinical Laboratory Genetic Tests Soar, as Members of Congress Debate How Patient Data Should be Handled, Secured, and Kept Private

Direct-to-consumer (DTC) genetic testing has been much in the news of late and clinical laboratories, anatomic pathology groups, and biomedical researchers have a stake in how the controversy plays out.

While healthcare consumers seem enamored with the idea of investigating their genomic ancestry in growing numbers, the question of how the data is collected, secured, and distributed when and to whom, is under increased scrutiny by federal lawmakers, bioethicists, and research scientists.

However, should public demand for DTC testing find support in Congress, some lab companies offering direct-to-consumer genetic tests could find their primary source of revenue curtailed.

DTC Sales Skyrocket as FDA Authorizes Genetic Tests for Certain Chronic Diseases

Dark Daily reported last fall on one company that had its plans to distribute thousands of free genetic tests at a football game suspended due to privacy concerns. (See, “State and Federal Agencies Throw Yellow Flag Delaying Free Genetic Tests at NFL Games in Baltimore—Are Clinical Laboratories on Notice about Free Testing?” October 13, 2017.)

Nevertheless, consumer demand for DTC tests continues to rise. In a press release, Ancestry, a family genetic history and consumer genomics company, reported:

  • Record sales of AncestryDNA kits during the 2017 four-day Black Friday to Cyber Monday weekend, selling more than 1.5 million kits; and,
  • The 2017 sales were triple the amount of kits sold during the same period in 2016.

Possibly helping the sale of DTC genetic tests may be the US Food and Drug Administration (FDA) authorization last year of 23andMe’s Personal Genome Service Genetic Health Risk tests for 10 diseases or conditions, including:

Senator Calls for Investigation of DTC Genetic Test Company Use of Patient Data

These are impressive sales. However, medical professionals may wonder how so much genetic data can be kept private by the testing companies. And medical laboratory leaders are not the only ones asking about privacy and the use of genetic test results.

In a November press conference, Senate Minority Leader Chuck Schumer called on the Federal Trade Commission (FTC) to look into genetic testing companies’ privacy and disclosure practices, noted NBC News.

“What those companies can do with all that data—your most sensitive and deepest info, your genetics—is not clear, and in some cases not fair and not right,” stated Schumer.

Congress took action in 2008 by passing the Genetic Information and Nondiscrimination Act (GINA), which bans employers and insurers from making decisions about people based on genetic predispositions to disease.

However, lawmakers also recently introduced House Bill 1313, the Preserving Employee Wellness Programs Act. It reads, in part, “… the collection of information about the manifested disease or disorder of a family member shall not be considered an unlawful acquisition of genetic information with respect to another family as part of a workplace wellness program offered by an employer ….”

“We’re injecting terrible opportunities for discrimination in the workplace,” Robert Green, MD, Professor of Medicine (Genetics) at Harvard Medical School, told Gizmodo.

Robert C. Green, MD, MPH

Robert C. Green, MD, MPH (above), Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital; Geneticist, Brigham and Women’s Hospital; and Director, Genomes2People Research Program at Brigham and Women’s Hospital, believes weak genetic privacy laws are inhibiting research and clinical care. “People decline genetic tests because of concerns over privacy and genetic discrimination, especially insurance discrimination,” he told Gizmodo. “This is stymying biomedical research and people’s access to healthcare.” (Photo copyright: Harvard Medical School.)

HIPAA Enables Selling of Anonymized Patient Genetic Data

Peter Pitts, former FDA Associate Commissioner, and President and Co-founder of the Center for Medicine in the Public Interest, a non-profit medical issues research group, blames the release of data by DTC genetic test companies on the Health Insurance Portability and Accountability Act (HIPAA), a law he says makes way for “anonymized” sale of patient data.

“The Portability Act was passed when genetic testing was just a distant dream on the horizon of personalized medicine,” Pitts wrote in a Forbes commentary. “But today that loophole has proven to be a cash cow. 23andMe has sold access to its database to at least 13 outside pharmaceutical firms … AncestryDNA recently announced a lucrative data-sharing partnership with the biotech company Calico.”

For its part, in an online privacy statement, 23andMe noted, “We will use your genetic information or self-reported information and share it with third parties for scientific research purposes only if you sign the appropriate consent document.”

Similarly, Ancestry points out in its posted privacy statement, “We share your genetic information with research partners only when you provide us with your express consent to do so through our informed consent to research.

Consumers Speak Out on Privacy; States Study Laws and Genetic Testing by Research Hospitals

How do consumers feel about the privacy of their genetic test data?  According to a news release, a survey by 23andMe found the following:

  • 80% of Americans are concerned about DNA testing privacy; however,
  • 88% have no awareness or understanding of what testing companies do to protect information; and,
  • 74% of people are, nonetheless, interested in genetic testing.

Meanwhile, as states promulgate various genetic privacy laws, a paper published at SSRN by researchers at the Massachusetts Institute of Technology (MIT) and the University of Virginia (UV) examined how different state laws affect patients’ decisions about having genetic testing performed at various research hospitals.

The MIT/UV study focused on genetic testing by research hospitals as opposed to the DTC genetic testing by private companies. The paper explained that states have one of three types of laws to protect patients’ privacy in genetic testing:

  • “Require the provider to notify the individual about potential privacy risks;
  • “Restrict discriminatory use of genetic data by employers or insurance companies; and,
  • “Limit redisclosure without consent.”

Findings, netted from more than 81,000 respondents, suggest:

  • When genetic data are explained in state laws as patient property, more tests are performed;
  • Conversely, state laws that focus on risk, and ask patients to consent to risk, lead to less people giving the go-ahead for genetic testing.

“We found a positive effect [on the number of tests] was an approach where you gave patients the potential to actually control their own data,” Catherine Tucker, PhD,  Distinguished Professor of Management at MIT and one of the study researchers, told MIT News.

Whether the provider of genetic tests is a private testing company or a research hospital’s clinical laboratory, privacy continues to be a concern, not just to physicians but to federal lawmakers as well. Nevertheless, healthcare consumers and patients who receive comprehensible information about how their genetic data may be used seem to be agreeable to it. At least for now, that is.

—Donna Marie Pocius

Related Information:

AncestryDNA Breaks Holiday Sales Record Black Friday to Cyber Monday

Senator Calls for More Scrutiny of Home DNA Test Industry

The Present and Future Asymmetry of Consumer Genetic Testing

Are Our Terrible Genetic Privacy Laws Hurting Science?

The Privacy Delusions of Genetic Testing

National Survey Shows Strong Interest in DNA Testing

Privacy Protection, Personalized Medicine, and Genetic Testing

How Privacy Policies Affect Genetic Testing

State and Federal Agencies Throw Yellow Flag Delaying Free Genetic Tests at NFL Games in Baltimore—Are Clinical Laboratories on Notice about Free Testing?

Human Antibodies in Medical Laboratory May Be Key to Immunity and Preventing Diseases Such as Influenza A

Scientists with Francis Crick Institute and Ragon Institute have successfully created human antibodies in vitro that can be made to recognize specific antigens in the human body; Could lead to new treatments for cancer and other infectious diseases

It’s been long-recognized that the ability to design human antibodies customized to recognize specific antigens could be a game-changer in the diagnosis and treatment of many diseases. It would enable the creation of useful new clinical laboratory tests, vaccines, and similar therapeutic modalities.

Now an international research team has published the findings of its novel technique that was developed to generate human antibodies in vitro. The research was conducted at the Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT), Harvard, and the Francis Crick Institute in London.

Antibodies and antigens are used in a large number of clinical laboratory and anatomic pathology tests and assays. In many cases, animal antibodies/antigens are used in test kits because they attract and bind to specific human antibodies/antigens that are biomarkers for diagnoses. Thus, as this technology is validated and further developed, it could be the source of useful biomarkers for lab tests as well as for vaccines.

Antibodies—also referred to as immunoglobulins—are made by the body’s B-lymphocytes (B cells) in response to antigens, such as bacteria, viruses, or other harmful substances. Each antibody has a special bearing on a particular antigen. For example, the human immunodeficiency virus (HIV) antibody and HIV antigen (p24) test screens and diagnoses people for HIV infection, explained LabTestsOnline.

Many medical laboratory tests use animal antibodies and antigens. But what if human antibodies could be generated and stimulated to recognize specific human antigens? That’s what the researchers believe they have done, according to a press release.

The Ragon Institute at MGH, MIT, and Harvard (above) was established in 2009 to find an HIV vaccine and to be a worldwide leader in the study of immunology. The Francis Crick Institute, formed in 2015, is a biomedical research institute using biology to understand health and disease. (Photo copyright: The Ragon Institute.)

The researchers know the novel technique they developed for generating human antibodies in vitro needs further development and validation. If this happens, the technique could one day be the source of useful biomarkers for medical lab tests, and may be a way to prevent infectious diseases.

“Specifically, it should allow the production of these antibodies within a shorter time frame in vitro and without the need for vaccination or blood/serum donation from recently infected or vaccinated individuals,” said Facundo D. Batista, PhD, in the press release. Batista is Principle Investigator with the Ragon Institute and led the research teams. “In addition, our method offers the potential to accelerate the development of new vaccines by allowing the efficient evaluation of candidate target antigens.”

Researchers Aim to Make Human Antibodies in Medical Laboratory

This international team of researchers sought to replicate in the lab—using patient blood samples—a natural human process for creation of antibodies from B cells. This is the process they wished to replicate:

·       Antibodies are made by the body’s B cells;

·       An antigen molecule is recognized by a B cell;

·       Plasma cells (able to secrete antibodies) develop;

·       An antibody binds to a particular antigen to fight an infection.

“B lymphocytes (B cells) play a critical role in adaptive immunity, providing protection from pathogens through the production of specific antibodies. B cells recognize and respond to pathogen-derived antigens through surface B cell receptors,” the researchers wrote in The Journal of Experimental Medicine (JEM).

Nanoparticles Key to the Approach

But finding an exact antigen is only one part of the B cell’s job. In the lab, B cells also need a trigger that enables them to grow and develop into plasma cells, which are key to fighting disease, the researchers noted.

“The in vitro activation of B cells in an antigen-dependent manner is difficult to achieve,” the authors stated in the JEM. “To overcome limitations, we developed a novel in vitro strategy to stimulate human B cells with streptavidin nanoparticles conjugated to both CpG and antigen. B cells producing antigen-specific antibodies were identified, quantified, and characterized to determine the antibody repertoire.”

According to the press release, “CpG oligonucleotides internalize into B cells that recognize the specific antigen.”

The statement, which garnered worldwide attention, noted the following steps taken by the researchers:

·       B cells from patient blood samples were isolated;

·       Then, they were treated with tiny nanoparticles coated with both CpG oligonucleotides and the right antigen;

·       These DNA molecules are unique, because they can activate toll-like receptor 9 (TLR9);

·       TLR9 develops into antibody-secreting plasma cells.

Results: Antibodies for Tetanus, Influenza, HIV

This method, according to the scientists, could be used in further research to develop antibodies to treat infectious diseases and cancer.

According to The Times of India,

·       “The team successfully demonstrated their approach using various bacterial and viral antigens, including the tetanus toxoid and proteins from several strains of influenza A;

·       “In each case, the researchers were able to produce specific, high-affinity antibodies in just a few days. Some of the anti-influenza antibodies generated by the technique recognized multiple strains of the virus and were able to neutralize its ability to infect cells;

·       “The procedure does not depend on the donors having been previously exposed to any of these antigens through vaccination or infection; and,

·       “Researchers were able to generate anti-HIV antibodies from B cells isolated from HIV-free patients.”

Research Suggests More Possibilities

While this highly scientific study may not be on the radar of most anatomic pathologists and medical laboratory leaders at the moment, it holds enormous promise to produce cures for infectious disease and more effective cancer treatments. This research project also demonstrates how new techniques using antibodies have the potential to create an entirely new generation of clinical laboratory assays that improve diagnostic accuracy and better inform physicians when they consider the most appropriate therapies for their patients.

—Donna Marie Pocius

Related Information:

Researchers Develop New Method to Generate Human Antibodies

Novel In Vitro Booster Vaccination to Rapidly Generate Antigen-Specific Human Monoclonal Antibodies

Human Antibodies Produced in Lab for First Time

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