Category Archives: Genetic Engineering

Over the last decade, as DNA-sequencing technology has grown ever faster and cheaper, our understanding of the human genome has increased accordingly. Yet scientists have until recently remained largely ham-fisted when theyve tried to directly modify genes in a living cell. Take sickle-cell anemia, for example. A debilitating and often deadly disease, it is caused by a mutation in just one of a patients three billion DNA base pairs. Even though this genetic error is simple and well studied, researchers are helpless to correct it and halt its devastating effects.

Now there is hope in the form of new genome-engineering tools, particularly one called CRISPR. This technology could allow researchers to perform microsurgery on genes, precisely and easily changing a DNA sequence at exact locations on a chromosome. Along with a technique called TALENs, invented several years ago, and a slightly older predecessor based on molecules called zinc finger nucleases, CRISPR could make gene therapies more broadly applicable, providing remedies for simple genetic disorders like sickle-cell anemia and eventually even leading to cures for more complex diseases involving multiple genes. Most conventional gene therapies crudely place new genetic material at a random location in the cell and can only add a gene. In contrast, CRISPR and the other new tools also give scientists a precise way to delete and edit specific bits of DNAeven by changing a single base pair. This means they can rewrite the human genome at will.

It is likely to be at least several years before such efforts can be developed into human therapeutics, but a growing number of academic researchers have seen some preliminary success with experiments involving sickle-cell anemia, HIV, and cystic fibrosis (see table below). One is Gang Bao, a bioengineering researcher at the Georgia Institute of Technology, who has already used CRISPR to correct the sickle-cell mutation in human cells grown in a dish. Bao and his team started the work in 2008 using zinc finger nucleases. When TALENs came out, his group switched quickly, says Bao, and then it began using CRISPR when that tool became available. While he has ambitions to eventually work on a variety of diseases, Bao says it makes sense to start with sickle-cell anemia. If we pick a disease to treat using genome editing, we should start with something relatively simple, he says. A disease caused by a single mutation, in a single gene, that involves only a single cell type.

In little more than a year, CRISPR has begun reinventing genetic research.

Bao has an idea of how such a treatment would work. Currently, physicians are able to cure a small percentage of sickle-cell patients by finding a human donor whose bone marrow is an immunological match; surgeons can then replace some of the patients bone marrow stem cells with donated ones. But such donors must be precisely matched with the patient, and even then, immune rejectiona potentially deadly problemis a serious risk. Baos cure would avoid all this. After harvesting blood cell precursors called hematopoietic stem cells from the bone marrow of a sickle-cell patient, scientists would use CRISPR to correct the defective gene. Then the gene-corrected stem cells would be returned to the patient, producing healthy red blood cells to replace the sickle cells. Even if we can replace 50 percent, a patient will feel much better, says Bao. If we replace 70 percent, the patient will be cured.

Though genome editing with CRISPR is just a little over a year old, it is already reinventing genetic research. In particular, it gives scientists the ability to quickly and simultaneously make multiple genetic changes to a cell. Many human illnesses, including heart disease, diabetes, and assorted neurological conditions, are affected by numerous variants in both disease genes and normal genes. Teasing out this complexity with animal models has been a slow and tedious process. For many questions in biology, we want to know how different genes interact, and for this we need to introduce mutations into multiple genes, says Rudolf Jaenisch, a biologist at the Whitehead Institute in Cambridge Massachusetts. But, says Jaenisch, using conventional tools to create a mouse with a single mutation can take up to a year. If a scientist wants an animal with multiple mutations, the genetic changes must be made sequentially, and the timeline for one experiment can extend into years. In contrast, Jaenisch and his colleagues, including MIT researcher Feng Zhang (a 2013 member of our list of 35 innovators under 35), reported last spring that CRISPR had allowed them to create a strain of mice with multiple mutations in three weeks.

Genome GPS

The biotechnology industry was born in 1973, when Herbert Boyer and Stanley Cohen inserted foreign DNA that they had manipulated in the lab into bacteria. Within a few years, Boyer had cofounded Genentech, and the company had begun using E. coli modified with a human gene to manufacture insulin for diabetics. In 1974, Jaenisch, then at the Salk Institute for Biological Studies in San Diego, created the first transgenic mouse by using viruses to spike the animals genome with a bit of DNA from another species. In these and other early examples of genetic engineering, however, researchers were limited to techniques that inserted the foreign DNA into the cell at random. All they could do was hope for the best.

It took more than two decades before molecular biologists became adept at efficiently changing specific genes in animal genomes. Dana Carroll of the University of Utah recognized that zinc finger nucleases, engineered proteins reported by colleagues at Johns Hopkins University in 1996, could be used as a programmable gene-targeting tool. One end of the protein can be designed to recognize a particular DNA sequence; the other end cuts DNA. When a cell then naturally repairs those cuts, it can patch its genome by copying from supplied foreign DNA. While the technology finally enabled scientists to confidently make changes where they want to on a chromosome, its difficult to use. Every modification requires the researcher to engineer a new protein tailored to the targeted sequencea difficult, time-consuming task that, because the proteins are finicky, doesnt always work.

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Genome Surgery

PUBLIC RELEASE DATE:

6-Feb-2014

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, February 6, 2014The ability to reprogram adult cells so they return to an undifferentiated, pluripotent statemuch like an embryonic stem cellis enabling the development of promising new cell therapies. Accelerating progress in this field will depend on identifying factors that promote pluripotency, such as the Brg1 protein described in a new study published in BioResearch Open Access, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the BioResearch Open Access website.

In "BRG1 Is Required to Maintain Pluripotency of Murine Embryonic Stem Cells," Nishant Singhal and coauthors, Max Planck Institute for Molecular Biomedicine, Mnster, and University of Mnster, Germany, demonstrate the critical role the Brg1 protein plays in regulating genes that are part of a network involved in maintaining the pluripotency of embryonic stem cells. This same network is the target for methods developed to reprogram adult somatic cells.

"This work further clarifies the role of the Brg1 containing BAF complex in regulating pluripotency and has important implications for all cellular reprogramming technologies," says BioResearch Open Access Editor Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

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About the Journal

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in promising areas of science and biomedical research, including, DNA and Cell Biology, Tissue Engineering, Stem Cells and Development, Human Gene Therapy, HGT Methods, and HGT Clinical Development, and AIDS Research and Human Retroviruses. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 80 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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Critical factor (BRG1) identified for maintaining stem cell pluripotency

Written by Patrick Dixon

Futurist Keynote - Articles and Videos - Biotechnology, Genetics, Gene Therapy, Stem Cells

Video on Genetic Engineering

Genetic engineering is the alteration of genetic code by artificial means, and is therefore different from traditional selective breeding.

Genetic engineering examples include taking the gene that programs poison in the tail of a scorpion, and combining it with a cabbage. These genetically modified cabbages kill caterpillers because they have learned to grow scorpion poison (insecticide) in their sap.

Genetic engineering also includes insertion of human genes into sheep so that they secrete alpha-1 antitrypsin in their milk - a useful substance in treating some cases of lung disease.

Genetic engineering has created a chicken with four legs and no wings.

Genetic engineering has created a goat with spider genes that creates "silk" in its milk.

Genetic engineering works because there is one language of life: human genes work in bacteria, monkey genes work in mice and earthworms. Tree genes work in bananas and frog genes work in rice. There is no limit in theory to the potential of genetic engineering.

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Genetic Engineering: What is Genetic Engineering?

Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or "knocked out", using a nuclease. Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations.

An organism that is generated through genetic engineering is considered to be a genetically modified organism (GMO). The first GMOs were bacteria in 1973; GM mice were generated in 1974. Insulin-producing bacteria were commercialized in 1982 and genetically modified food has been sold since 1994. Glofish, the first GMO designed as a pet, was first sold in the United States December in 2003.[1]

Genetic engineering techniques have been applied in numerous fields including research, agriculture, industrial biotechnology, and medicine. Enzymes used in laundry detergent and medicines such as insulin and human growth hormone are now manufactured in GM cells, experimental GM cell lines and GM animals such as mice or zebrafish are being used for research purposes, and genetically modified crops have been commercialized.

IUPAC definition

Process of inserting new genetic information into existing cells in order to modify a specific organism for the purpose of changing its characteristics.

Note: Adapted from ref.[2]

[3]

Genetic engineering alters the genetic makeup of an organism using techniques that remove heritable material or that introduce DNA prepared outside the organism either directly into the host or into a cell that is then fused or hybridized with the host.[4] This involves using recombinant nucleic acid (DNA or RNA) techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macro-injection and micro-encapsulation techniques.

Genetic engineering does not normally include traditional animal and plant breeding, in vitro fertilisation, induction of polyploidy, mutagenesis and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process.[4] However the European Commission has also defined genetic engineering broadly as including selective breeding and other means of artificial selection.[5]Cloning and stem cell research, although not considered genetic engineering,[6] are closely related and genetic engineering can be used within them.[7]Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesized genetic material from raw materials into an organism.[8]

If genetic material from another species is added to the host, the resulting organism is called transgenic. If genetic material from the same species or a species that can naturally breed with the host is used the resulting organism is called cisgenic.[9] Genetic engineering can also be used to remove genetic material from the target organism, creating a gene knockout organism.[10] In Europe genetic modification is synonymous with genetic engineering while within the United States of America it can also refer to conventional breeding methods.[11][12] The Canadian regulatory system is based on whether a product has novel features regardless of method of origin. In other words, a product is regulated as genetically modified if it carries some trait not previously found in the species whether it was generated using traditional breeding methods (e.g., selective breeding, cell fusion, mutation breeding) or genetic engineering.[13][14][15] Within the scientific community, the term genetic engineering is not commonly used; more specific terms such as transgenic are preferred.

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Genetic engineering - Wikipedia, the free encyclopedia

Public release date: 10-Jun-2013 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, June 10, 2013The Genetics Policy Institute (GPI) and Mary Ann Liebert, Inc., publishers have announced that the 2013 World Stem Cell Report will be published as a special supplement to the peer-reviewed journal Stem Cells and Development. Dr. Graham Parker and Bernard Siegel will serve as Co-Editors-in-Chief, joined by Rosario Isasi (McGill University) as Managing Editor.

It was also announced that Mary Ann Liebert, Inc., publishers and Genetic Engineering & Biotechnology News (GEN), a Liebert publication, will become joint platinum media sponsors of the GPI's 2013 World Stem Cell Summit that will take place at the Manchester Grand Hyatt San Diego, December 4 in San Diego, CA.

Bernard Siegel, Executive Director of GPI and Founder and Co-chair of the Summit said, "We are proud to partner with Graham Parker and the skilled editorial team at Stem Cells and Development to publish our annual Report. The Journal's extensive audience, combined with the reach of the community attending and supporting the World Stem Cell Summit, will allow our readership to expand exponentially. We will continue to provide an array of specialized articles offering unique insights of leading policy-makers, regulators, and experts in law, ethics, advocacy, industry, and philanthropy from countries, regions, and states. The Report fills a critical unmet need by providing a global framework for all stakeholders."

Mary Ann Liebert, publisher & CEO of both Stem Cells and Development and GEN stated, "We are delighted to be working with a key thought leader and senior statesman for the field, Bernie Siegel, and his GPI team on this important collaboration. The World Stem Cell Report delivers an orbital and unique viewpoint, with content that is timely, comprehensive, and direct. We are proud to add this important annual publication to our many journals that intersect the world of regenerative medicine."

GEN Editor-in-Chief John Sterling stated, "The World Stem Cell Summit is the critical global meeting, providing the best opportunity for the GEN community to participate in the world of regenerative medicine. Our platinum media sponsorship allows GEN readers, both in print and online, and advertisers to have a front row seat to listen and learn from the top experts on the very dynamic and expertly conceptualized Summit platform."

The Report will be made available to all subscribers of Stem Cells and Development and complimentary to attendees of the World Stem Cell Summit. The Summit program delivers on the "big picture" featuring 170+ prominent scientists, business leaders, regulators, policy-makers, advocates, economic development officers, experts in law and ethics, and visionary gurus who will discuss the latest scientific discoveries, business models, legal and regulatory solutions, and best practices. The Summit is expected to attract attendees from more than 40 nations.

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World Stem Cell Summit to be presented by Genetics Policy Institute, Mary Ann Liebert, Inc., and Genetic Engineering ...

MADISON, Wis., June 5, 2013 /PRNewswire/ --Cellular Dynamics International (CDI) today announced that it has expanded its MyCell Products line, offering access to a number of human disease models and licensing key genetic engineering patents from Life Technologies and Sigma-Aldrich. CDI's MyCell Products include custom cell products manufactured using induced pluripotent stem cell (iPSC) technology to make stem cells or differentiated cells from any individual, including those with diseases of interest to pharmaceutical and academic researchers.

CDI's MyCell Products now offer access to a number of disease models, including cardiomyopathies and arrhythmias, vision disorders, neurological disorders, and muscular dystrophies. In addition, the company is actively working on expanding its disease model offering, currently working on additional disease models for neurodegenerative disorders and drug-induced liver injury (DILI).

Within the MyCell Products line, CDI maintains the iPSC line of each of the disease models, enabling customers to request manufacture of differentiated cells, such as cardiomyocytes, neurons, hepatocytes, and endothelial cells, for their discovery research.

In addition, CDI has licensed Life Technologies' GeneArt Precision TALs (TALENs) and Sigma's CompoZr ZFN technologies, which act like genomic scissors to cut DNA in a precise location. These nuclease technologies facilitate efficient genomic editing by creating double-stranded breaks in DNA at user-specified locations, stimulating the cell's natural repair process and enabling targeted gene insertions, deletions, or modifications. CDI will use the TALENs and ZFN technologies to perform genetic engineering specified by the customer, for example to introduce or correct a specific mutation, thus creating human disease models and isogenic controls.

"This expansion of the MyCell Products line is the next step in our growing disease-in-a-dish portfolio and allows our customers more ready access to diseases of interest from our growing catalog of iPSCs," said Chris Parker, CDI chief commercial officer. "Through the MyCell Products line, researchers can now access human disease models either through creation of iPSC-derived cells directly from a patient, or through inducing a disease state via use of these TALEN or ZFN technologies."

Bob Palay, CDI chief executive officer, said, "CDI's commercial goal has been to provide access to human cells that reproduce human biology, and we see both of these developments as steps toward achieving that goal. We're pleased to license these nuclease technologies from Life Technologies and Sigma-Aldrich, and the combination of these nuclease technologies with CDI's iPSC-derived cells creates a new, powerful tool to better understand and target human disease."

About Cellular Dynamics International, Inc.Cellular Dynamics International, Inc. (CDI) is a leading developer of stem cell technologies for in vitro use in drug discovery, toxicity testing and chemical safety, in vivo and cell-based therapeutic research and stem cell banking. CDI harnesses its unique manufacturing technology to produce differentiated tissue cells in industrial quality, quantity and purity from any individual's stem cell line created from a standard blood draw. CDI was founded in 2004 by Dr. James Thomson, a pioneer in human pluripotent stem cell research at the University of Wisconsin-Madison. CDI's facilities are located in Madison, Wisconsin. CDI's headquarters are located in Madison, Wisconsin, with a second facility in Novato, California. See http://www.cellulardynamics.com.

Follow us on Twitter @CellDynamics or http://www.twitter.com/celldynamics

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Cellular Dynamics International Expands MyCell Products Line with Disease Models, Genetic Engineering Patents

When scientists Phillipe Horvath and Rodolphe Barrangou set out to find a better way to make yogurt, they didn't expect to stumble across one of the future's most promising discoveries: a super protein that can accurately cut DNAand could perhaps revolutionize genetic engineering.

The protein, called Cas9, can be exploited to snip strands of DNA in exactly the place researchers want. It doesn't make genetic engineering easy, but does make it much, much easieras it allows researchers to splice sequences of DNA together affordably, with unprecedented accuracy.

So how does it work? Well, Cas9 was found last year to join forces with bacteria in such a way that, combined, they home into viruses and kill them by cutting their DNA at specific, targeted points. That's interestingin fact, it made it a prime candidate for making yogurt production more efficient.

But what's more interesting is that Cas9 can be paired with any string of RNAstrings of molecules not unlike DNA which code and regulate gene expressionto target a matching piece of DNA and snip it with incredible accuracy. Kind of like a pair of tiny, custom DNA scissors. That's not interestingthat's amazing.

Now, though, reports Forbes, the world of biology is swarming over Cas9 and the possibilities it affords. George Church of Harvard University explains:

"It is spreading like wildfire from everyone who knows about it and it certainly is very tantalizing. It's easy to get in and start doing lots of experiments."

The embrace of Cas9 could bring with it massive advances, then. Not least the ability to study genetics in ways never before possible. Forbes explains:

[S]ay there are three changes in the DNA in or around a gene that might cause a disease. Right now, it's hard to study them directly. But now, Church says, you could take a cell from a person who has already had their DNA sequenced, as he is doing with his Personal Genome Project. Then you'd create what's known as an induced pluripotent stem cell, a cell that behaves much like one in an embryo. After that, you could use Cas9 to change each of those DNA spelling changes.

There is, of course, still a long way to gothis research is being conducted in Petri dishes right now, not living creaturesbut it's a long time since a single protein had the entire world of biology so excited. It's only a matter of time before something major comes of it; not bad, for a protein which was originally discovered to make better yogurt. [Forbes, Science]

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The Super Protein That Can Cut DNA and Revolutionize Genetic Engineering

Ramble: Simelweis Taboo
I just don #39;t understand narrowmindedness. I don #39;t understand the stubborn refusal to face reality with integrity. I don #39;t understand cowardice. We each have only one life. Why squander it on timidity, prejudice and just so stories? Video referenced: "Taboos of Science" scishow youtu.be " Published on Jul 30, 2012 Hank discusses some of the taboos which have plagued scientific inquiry in the past and a few that still exist today. Like SciShow? http://www.facebook.com Follow SciShow: http://www.twitter.com References: dft.ba This video contains the following sounds from Freesound.org: "grim fart.wav" by Walter_Odington "Toilet Flush.wav" by tweeterdj science, scishow, taboo, society, culture, research, study, ignaz semmelweis, germ theory, disease, louis pasteur, antiseptic, social norms, semmelweis reflex, dean radin, noetic science, stem cell, chimaera, human cloning, clone, dolly, sheep, ethics, religion, panayiotis zavos, synthetic biology, genetic engineering, biology, genetics, mental health, gender identity, gender dysphoria, sexual orientation, physics, archaeology, human remains, spirituality, consciousness, poop, toilet, sanitation"From:rriverstone1Views:39 5ratingsTime:15:28More inPeople Blogs

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Ramble: Simelweis Taboo - Video

Genetic Engineering Of Mesenchymal Stem Cells
ll4.me Genetic Engineering Of Mesenchymal Stem Cells 1. Mesenchymal Stem Cell Engineering and Transplantation: An introduction; F. Aerts, G. Wagemaker- 2. Establishment and Transduction of primary human Stromal/Mesenchymal Stem Cell Monolayers; T. Meyerrose, I. Rosova, m. Dao, P. Herrbrich, G. Bauer, JA Nolta- 3. Gene Expression Profiles of Mesenchymal Stem Cells; DG Phinney- 4. In Vivo Homing and Regeneration of freshly isolated and culture Murine Mesenchymal Stem Cells; RE Ploemacher- 5. Non-human primate models of Mesenchymal Stem Cell Transplantation; SM Devine, R. Hoffman- 6. Engineering of Human Adipose-derived Mesenchymal Stem-like Cells; JK Fraser, M. Zhu, B. Strem, MH Hedrick- 7. Uncommitted Progenitors in Cultures of Bone Marrow-derived Mesenchymal Stem Cells; JJ Minguell, A. Rices, WD Sierralta- 8. Bone Marrow Mesenchymal Stem Cell Transplantation for Children with severe Osteogenesis Imperfecta; EM Horwitz, PL Gordon- 9. Clinical Trials of Human Mesenchymal Stem Cells to support Hematopoietic Stem Cell Transplantation; ON Ko EAN/ISBN : 9781402039591 Publisher(s): Springer Netherlands Discussed keywords: Stammzelle Format: ePub/PDF Author(s): Nolta, Jan A. 1. Mesenchymal Stem Cell Engineering and Transplantation: An introduction; F. Aerts, G. Wagemaker- 2. Establishment and Transduction of primary human Stromal/Mesenchymal Stem Cell Monolayers; T. MeyerFrom:jonibishop696Views:0 0ratingsTime:00:12More inPeople Blogs

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Genetic Engineering Of Mesenchymal Stem Cells - Video

Public release date: 16-Nov-2012 [ | E-mail | Share ]

Contact: Vicki Cohn vcohn@liebertpub.com 914-740-2100 x2156 Mary Ann Liebert, Inc./Genetic Engineering News

New Rochelle, NY, November 15, 2012Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and a risk for serious disease in liver transplant recipients. Molecular tests that can identify early protein markers produced by EBV may have value for diagnosing active infection. The benefits of this diagnostic approach in patients with mononucleosis and in EBV-infected transplant patients are evaluated in an article published in BioResearch Open Access, a bimonthly peer-reviewed open access journal from Mary Ann Liebert, Inc., publishers. The article is available free on the BioResearch Open Access website.

Andrea Crowley, Jeff Connell, Kirsten Schaffer, William Halla, and Jaythoon Hassan, University College Dublin and St. Vincent's University Hospital, Dublin, Ireland, compared three immunoassay methods for detecting antibodies produced by the body in response to EBV infection and the presence of proteins that comprise the EBV early antigen complex. The researchers determined which of the diagnostic tests could better predict EBV infection in patients with mononucleosis or in immunosuppressed adult liver transplant recipients. The article "Is There Diagnostic Value in Detection of Immunoglobulin G Antibodies to the EpsteinBarr Virus Early Antigen?" presents the complete methodology and results of this study.

"Having the ability to predict the risk of developing EBV-induced lymphoproliferative disorders after a transplant has important consequences for patient care, as it would allow for prompt therapy and could potentially decrease patient mortality," says Editor-in-Chief Jane Taylor, PhD, MRC Centre for Regenerative Medicine, University of Edinburgh, Scotland.

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About the Journal

BioResearch Open Access is a bimonthly peer-reviewed open access journal that provides a new rapid-publication forum for a broad range of scientific topics including molecular and cellular biology, tissue engineering and biomaterials, bioengineering, regenerative medicine, stem cells, gene therapy, systems biology, genetics, biochemistry, virology, microbiology, and neuroscience. All articles are published within 4 weeks of acceptance and are fully open access and posted on PubMedCentral. All journal content is available on the BioResearch Open Access website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, Human Gene Therapy and HGT Methods, and AIDS Research and Human Retroviruses. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry's most widely read publication worldwide. A complete list of the firm's 70 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.

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Is the detection of early markers of Epstein Barr virus of diagnostic value?