Category Archives: Genetic Engineering

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Kat J. McAlpine katherine.mcalpine@wyss.harvard.edu 617-432-8266 Wyss Institute for Biologically Inspired Engineering at Harvard @wyssinstitute

(BOSTON) -- Stem cells offer great potential in biomedical engineering due to their pluripotency, which is the ability to multiply indefinitely and also to differentiate and develop into any kind of the hundreds of different cells and bodily tissues. But the precise complexity of how stem cell development is regulated throughout states of cellular change has been difficult to pinpoint until now.

By using powerful new single-cell genetic profiling techniques, scientists at the Wyss Institute for Biologically Inspired Engineering and Boston Children's Hospital have uncovered far more variation in pluripotent stem cells than was previously appreciated. The findings, reported today in Nature, bring researchers closer to a day when many different kinds of stem cells could be leveraged for disease therapy and regenerative treatments.

"Stem cell colonies contain much variability between individual cells. This has been considered somewhat problematic for developing predictive approaches in stem cell engineering," said the study's co-senior author James Collins, Ph.D., who is a Wyss Institute Core Faculty member, the Henri Termeer Professor of Medical Engineering & Science at MIT, and a Professor of Biological Engineering at MIT. "Now, we have discovered that what was previously considered problematic variability could actually be beneficial to our ability to precisely control stem cells."

The research team has learned that there are many small fluctuations in the state of a stem cell's pluripotency that can influence which developmental path it will follow.

It's a very fundamental study but it highlights the wide range of states of pluripotency," said George Daley, study co-senior author, Director of Stem Cell Transplantation at Boston Children's Hospital and a Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School. "We've captured a detailed molecular profile of the different states of stem cells."

Taking this into account, researchers are now better equipped to manipulate and precisely control which cell and tissue types will develop from an individual pluripotent stem cell or stem cell colony.

"The study was made possible through the use of novel technologies for studying individual cells, which were developed in part by collaborating groups at the Broad Institute, giving our team an unprecedented view of stem cell heterogeneity at the individual cell level," said Patrick Cahan, co-lead author on the study and Postdoctoral Fellow at Boston Children's Hospital and Harvard Medical School.

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New single-cell analysis reveals complex variations in stem cells

PUBLIC RELEASE DATE:

4-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 4, 2014--Recommendations by physician groups to avoid bedsharing among mothers and their babies are intended to reduce sleep-related infant deaths. But evidence suggests that the risks of bedsharing have been over-emphasized, advice never to bedshare is unrealistic, and avoiding bedsharing may interfere with breastfeeding, according to an article in Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine published by Mary Ann Liebert, Inc., publishers. The article is available free on the Breastfeeding Medicine website at http://online.liebertpub.com/doi/full/10.1089/bfm.2014.0113 until January 4, 2015.

In "Speaking Out on Safe Sleep: Evidence-Based Infant Sleep Recommendations, Melissa Bartick, MD, MSC, Cambridge Health Alliance and Harvard Medical School (Cambridge, MA), and Linda Smith, MPH, IBCLC, Boonshoft School of Medicine, Wright State University (Dayton, OH), discuss the American Academy of Pediatrics' (AAP) recommendations against all bedsharing for sleep, the leading modifiable risk factors for preventing Sudden Infant Death Syndrome (SIDS), and the potential for the AAP's bedsharing recommendations to interfere with the frequency, duration, and exclusivity of breastfeeding.

"The alternatives to feeding an infant in bed, such as on a couch, lounge chair, or rocker are far greater risks for SIDS," says Ruth Lawrence, MD, Editor-in-Chief of Breastfeeding Medicine and Professor of Pediatrics, University of Rochester School of Medicine. "Bed-sharing increases the risk of SIDS when the infant is bottle fed or the mother is obese or impaired by smoking, alcohol, or illicit drugs. These are correctable risks of SIDS. Breastfeeding is protective, and the editors of Breastfeeding Medicine are pleased that the AAP Task Force on SIDS is strongly supporting breastfeeding."

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About the Journal

Breastfeeding Medicine, the official journal of the Academy of Breastfeeding Medicine, is an authoritative, peer-reviewed, multidisciplinary journal published 10 times per year in print and online. The Journal publishes original scientific papers, reviews, and case studies on a broad spectrum of topics in lactation medicine. It presents evidence-based research advances and explores the immediate and long-term outcomes of breastfeeding, including the epidemiologic, physiologic, and psychological benefits of breastfeeding. Tables of content and a sample issue may be viewed on the Breastfeeding Medicine website at http://www.liebertpub.com/bfm.

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Recommendations against mother-infant bedsharing interfere with breastfeeding

PUBLIC RELEASE DATE:

3-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 3, 2014--Hereditary angioedema (HAE), a rare genetic disease that causes recurrent swelling under the skin and of the mucosal lining of the gastrointestinal tract and upper airway, usually first appears before 20 years of age. A comprehensive review of the therapies currently available to treat HAE in adults shows that some of these treatments are also safe and effective for use in older children and adolescents. Current and potential future therapies are discussed in a Review article in a special issue of Pediatric Allergy, Immunology, and Pulmonology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the Pediatric Allergy, Immunology, and Pulmonology website at http://online.liebertpub.com/doi/full/10.1089/ped.2014.0412 until January 3, 2015.

Based on the current medical literature, Eveline Wu, University of North Carolina at Chapel Hill, and Michael Frank, Duke University Medical Center (Durham, NC), report that additional therapies are now approved for use in the pediatric age group. In their article "Management of Hereditary Angioedema in Childhood: A Review" they also discuss clinical trials and published experience among younger age groups for which data are most limited.

"HAE is a potentially life-threatening disease that until recently had very limited therapeutic options for children," says Pediatric Allergy, Immunology, and Pulmonology Editor-in-Chief Mary Cataletto, MD, Professor of Clinical Pediatrics, State University of New York at Stony Brook (Stony Brook, NY). "This special issue of Pediatric Allergy, Immunology, and Pulmonology, developed in collaboration with Guest Editor Dr. Timothy Craig, has been created for physicians who care for children. It focuses on recent advances in HAE-related immunophysiology, as well as current and future therapies for acute and chronic care and prophylaxis."

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About the Journal

Pediatric Allergy, Immunology, and Pulmonology is a quarterly, peer-reviewed journal published in print and online. The Journal synthesizes the pulmonary, allergy, and immunology communities in the advancement of the respiratory health of children. The Journal provides comprehensive coverage to further the understanding and optimize the treatment of some of the most common and costly chronic illnesses in children. It includes original translational, clinical, and epidemiologic research; public health, quality improvement, and case control studies; patient education research; and the latest research and standards of care for functional and genetic immune deficiencies and interstitial lung diseases. Tables of content and a sample issue may be viewed on the Pediatric Allergy, Immunology, and Pulmonology website at http://www.liebertpub.com/ped.

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Are there safe and effective treatments for hereditary angioedema in children?

Cyrus Co. Genetic Engineering Episode 1(E.G.C.)
This facility was funded by Coronia Corp. No hate mail.

By: E.G.C. Cyrus and Friends

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Cyrus Co. Genetic Engineering Episode 1(E.G.C.) - Video

By Isaac Fletcher, contributing writer, Food Online

J.R. Simplots Innate potato may provide potential health benefits through genetic engineering, but uncertainty over long-term risks and degree of benefits raise some concerns

The U.S. Department of Agriculture (USDA) has recently approved for commercial planting a potato that has been genetically engineered to reduce the amounts of a potentially harmful ingredient that appear in French fries and potato chips. When potatoes are fried, a chemical called acrylamide, which is suspected of causing cancer, is produced. The genetic engineering involves altering the potatos DNA so that when the potato is fried, the amount of acrylamide that appears is reduced. Additionally, the genetically-engineered potato is resistant to bruising. This will help potato growers and processors lower the instances of damage during shipping and storage, leading to fewer occurrences of lost value and unusable product. The potatoes have been developed by the J.R. Simplot Company of Boise, Idaho, a major supplier of McDonalds frozen French fries.

Rather than solely providing benefit to farmers and producers, the potato is among a new wave of genetically-engineered crops designed to provide benefits to consumers. However, with many consumers calling into question the safety of genetically-modified foods, the new potato may face some challenges in winning over consumer approval. Such consumer concerns raise questions about whether the potatoes will be used by various food companies and restaurant chains.

In the 1990s, genetically-modified potatoes were introduced by Monsanto in an effort to provide resistance against the Colorado potato beetle. However, the market crumbled when major buyers of potatoes instructed suppliers to not grow them due to fears over consumer resistance. However, the new potato from Simplot has some advantages that may help it weather the tide of consumer uncertainty.

First of all, the potato aims to provide potential health benefits to consumers rather than just providing cost-savings to suppliers and producers. Furthermore, Simplot is a well-established power in the potato industry and has likely been laying the foundation for product acceptance among its customers. The other strength of Simplots potato is that, unlike many other genetically-engineered crops, the potatoes do not contain genes from any other species, instead, the potato contains fragments of potato DNA that serve to mute four of the potatoes own genes involved in the production of particular enzymes. For this reason, Simplot has chosen to call its product the Innate potato, an innocuous name that may help win over consumer acceptance. Haven Baker, head of potato development at Simplot, explains, We are trying to use genes from the potato plant back into the potato plant. We believe theres some more comfort in that.

However, that is not to say that the Innate potato will not face roadblocks along the way. There are some questions over the long-term effects of this kind of engineering and, according to Doug Gurian-Sherman, a plant pathologist and senior scientist at the Center for Food Safety, much about RNA interference the technique used to mute the genes is not fully understood. Gurian-Sherman argues, We think this is a really premature approval of a technology that is not being adequately regulated. Additionally, the benefits of reducing acrylamide levels by 50 to 75 percent are still unclear.

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USDA Gives Genetically-Engineered Potatoes The Thumbs Up

PUBLIC RELEASE DATE:

2-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 2, 2014--A study of active duty U.S. Marines who suffered a recent or previous concussion(s) examined whether persistent post-concussive symptoms (PPCS) and lingering effects on cognitive function are due to concussion-related brain trauma or emotional distress. The results are different for a recent concussion compared to a history of multiple concussions, according to the study published in Journal of Neurotrauma, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available Open Access on the Journal of Neurotrauma website at http://online.liebertpub.com/doi/full/10.1089/neu.2014.3363.

James Spira, U.S. Department of Veterans Affairs and University of Hawaii (Honolulu, HI), Corinna Lathan, AnthroTronix, Inc. (Silver Spring, MD), Joseph Bleiberg, Walter Reed National Military Medical Center (Bethesda, MD), and Jack Tsao, U.S. Navy Bureau of Medicine and Surgery (Falls Church, VA), assessed the effects of concussion on persistent symptoms, independent of deployment history, combat exposure, and symptoms of post-traumatic stress disorder and depression. They describe the results for persons with a recent concussion or who had ever had a concussion to those who had more than one lifetime concussion in the article "The Impact of Multiple Concussions on Emotional Distress, Post-Concussive Symptoms, and Neurocognitive Functioning in Active Duty United States Marines Independent of Combat Exposure or Emotional Distress".

John T. Povlishock, PhD, Editor-in-Chief of Journal of Neurotrauma and Professor, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, notes that "This study by Spira and colleagues represents an important contribution to our understanding of the negative impact of multiple concussions in a relatively large military population sustaining both deployment and non-deployment related trauma. The consistent observation that multiple concussive injuries are associated with worse emotional and post-concussive symptoms is an extremely important finding that must guide our evaluation of individuals, in both the military and civilian settings, who have sustained multiple concussive injuries. While the authors acknowledge some limitations of the current work and the need for future research to follow a similar cohort in terms of the time course and causality of the symptoms associated with concussion, overall this well done study adds significantly to our increased understanding of the adverse consequences of repetitive concussive/mild traumatic brain injury."

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About the Journal

Journal of Neurotrauma is an authoritative peer-reviewed journal published 24 times per year in print and online that focuses on the latest advances in the clinical and laboratory investigation of traumatic brain and spinal cord injury. Emphasis is on the basic pathobiology of injury to the nervous system, and the papers and reviews evaluate preclinical and clinical trials targeted at improving the early management and long-term care and recovery of patients with traumatic brain injury. Journal of Neurotrauma is the official journal of the National Neurotrauma Society and the International Neurotrauma Society. Complete tables of content and a sample issue may be viewed on the Journal of Neurotrauma website at http://www.liebertpub.com/neu.

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Do concussions have lingering cognitive, physical, and emotional effects?

PUBLIC RELEASE DATE:

2-Dec-2014

Contact: Kathryn Ryan kryan@liebertpub.com 914-740-2100 Mary Ann Liebert, Inc./Genetic Engineering News @LiebertOnline

New Rochelle, NY, December 2, 2014--The challenges in providing psychotherapy to individuals with autism spectrum disorders (ASD) who also are struggling with their gender identity are explored in two case studies of high-functioning persons with diagnoses of ASD and gender dysphoria (GD). The authors describe the unique complexities presented by these two diagnoses and offer suggested techniques for helping these individuals explore their gender identities in an article in LGBT Health, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. The article is available free on the LGBT Health website until January 2, 2015.

New York, NY-based psychotherapist Laura A. Jacobs, LCSW, and coauthors from New York University and private practice explain why characteristics of ASD, such as the limited ability to express feelings, difficulty with social interaction and impaired theory of mind, as well as the intolerance of ambiguity, may present special difficulties for gender identity formation in persons with GD. However, in the article "Gender Dysphoria and Co-Occurring Autism Spectrum Disorders: Review, Case Examples, and Treatment Considerations," the authors suggest that high-functioning individuals with ASDs and GD can be good candidates for gender transition and can benefit from it.

"While much has been written recently on the co-occurrence of GD and ASDs, few case histories or papers discussing treatment have been published to date, gaps that this article addresses," says Editor-in-Chief William Byne, MD, PhD, Icahn School of Medicine at Mount Sinai, New York, NY. "The article also underscores that while the presence of an autism spectrum disorder poses particular issues that must be addressed, it does not preclude gender transition."

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About the Journal

Spanning a broad array of disciplines LGBT Health, published quarterly online with Open Access options and in print, brings together the LGBT research, health care, and advocacy communities to address current challenges and improve the health, well-being, and clinical outcomes of LGBT persons. The Journal publishes original research, review articles, clinical reports, case studies, legal and policy perspectives, and much more. Complete tables of content and a sample issue may be viewed on the LGBT Health website.

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Combination of autism spectrum disorder and gender nonconformity presents unique challenges

Dec 02, 2014 by Bendta Schroeder

Before DNA can be transcribed into RNA, an early step in turning the genetic template into protein, the nucleus must first assemble a molecular machine called the pre-initiation complex (PIC), capable of unzipping the double helix and loading the DNA onto the transcription enzyme.

The PIC's dozens of parts are scattered throughout a dense nucleus, packed with DNA, proteins, and other biomolecules. Transcription factors and enzymes must find their way to the transcription site, driven by weak and transient interactions, to be assembled into a living, working machine. The assembly can happen in a matter of seconds.

Weak and transient interactions are thought to propel, not just transcription, but the majority of vital cell processes. In these interactions, biomolecules join and disband easily, allowing them to act collectively and quickly in response to the needs of the cell. But exactly how these interactions work is a mystery.

Ibrahim Ciss, assistant professor of physics, wants to solve this mystery, molecule by molecule, in living cells, in real time.

"This is probably one of the most spectacular examples in nature where the interactions of individual biomolecules give rise to something we don't yet understandthe emergence of life," Ciss says.

Transcription, molecule by molecule

For Ciss to follow transcription as it unfolds, he would have to circumvent the limitations of conventional techniques for studying biomolecules. Biochemical techniques that isolate molecules in test tubes or label them in fixed cells destroy the conditions that make weak and transient interactions possible. Light microscopy can preserve those conditions, but most biomolecules are too small and interact too closely to be distinguished with the light diffraction limit of 200 nanometers.

Instead, Ciss uses tools from physics to illuminate the transcription process at high resolution. For example, he adapted a new fluorescent imaging technique called photoactivation localization microscopy (PALM). PALM activates fluorescent tagging proteins at random and then applies a statistical algorithm to determine the exact location of each protein with nanometer-accuracy within the pixel of light. When Ciss repeats the process at high speed and volume, he can map the precise location of tagged biomolecules as they cluster at a transcription site or trace the path of a single transcription factor as it moves across the nucleus. Furthermore, by developing a temporal correlation method coupled with PALM, called tcPALM, Ciss can get direct access to the clustering dynamics for the first time.

Recently, Ciss used tcPALM to show that the transcriptional enzyme RNA Polymerase II (Pol II) clusters for just a few seconds as transcription begins. The result is surprising, given that it takes several minutes for a full RNA sequence to be synthesized. When Ciss suppressed and then reactivated transcription just before imaging, he observed Pol II clustering at unusually high concentrations. When he blocked Pol II from escaping the promoter and transcribing the DNA, the cluster of Pol II around the promoter didn't dissipate.

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Unraveling the mystery of DNA transcription, one molecule at a time

13 hours ago Streptococcus pyogenes is one of the bacteria in which the HZI scientists have studied the CRISPR-Cas system. Credit: HZI / M. Rohde

Genome engineering with the RNA-guided CRISPR-Cas9 system in animals and plants is changing biology. It is easier to use and more efficient than other genetic engineering tools, thus it is already being applied in laboratories all over the world just a few years after its discovery. This rapid adoption and the history of the system are the core topics of a review published in the renowned journal Science. The review was written by the discoverers of the system Prof. Emmanuelle Charpentier, who works at the Helmholtz Centre for Infection Research (HZI) and is also affiliated to the Hannover Medical School and Ume University, and Prof. Jennifer Doudna from the University of California, Berkeley, USA.

Many diseases result from a change of an individual's DNA - the letter code that genes consist of. The defined order of the letters within a gene usually codes for a protein. Proteins are the workforce of our body and responsible for almost all processes needed to keep us running. When a gene is altered, its protein product may lose its normal function and disorders can result. "Making site-specific changes to the genome therefore is an interesting approach to preventing or treating those diseases", says Prof Emmanuelle Charpentier, head of the HZI research department "Regulation in Infection Biology". Due to this, ever since the discovery of the DNA structure, researchers have been looking for a way to alternate the genetic code.

First techniques like zinc finger nucleases and synthetic nucleases called TALENs were a starting point but turned out to be expensive and difficult to handle for a beginner. "The existing technologies are dependent on proteins as address labels and customizing new proteins for any new change to introduce in the DNA is a cumbersome process", says Charpentier. In 2012, while working at Ume University, she described what is now revolutionising genetic engineering: the CRISPR-Cas9 system.

It is based on the immune system of bacteria and archaea but is also of value in the laboratory. CRISPR is short for Clustered Regularly Interspaced Palindromic Repeats, whereas Cas simply stands for the CRISPR-associated protein. "Initially we identified a novel RNA, namely tracrRNA, associated to the CRISPR-Cas9 system, which we published in 2011 in Nature. We were excited when Krzysztof Chylinski from my laboratory subsequently confirmed a long term thinking: Cas9 is an enzyme that functions with two RNAs", says Charpentier.

Together the system has the ability to detect specific sequences of letters within the genetic code and to cut DNA at a specific point. In this process the Cas9 protein functions as the scissors and an RNA snippet as the address label ensuring that the cut happens in the right place. In collaboration with Martin Jinek and Jennifer Doudna, the system could be simplified to use it as a universal technology. Now the user would just have to replace the sequence of this RNA to target virtually any sequence in the genome.

After describing the general abilities of CRISPR-Cas9 in 2012 it was shown in early 2013 that it works as efficiently in human cells as it does in bacteria. Ever since, there has been a real hype around the topic and researchers from all over the world have suggested new areas in which the new tool can be used. The possible applications extend from developing new therapies for genetic disorders caused by gene mutations to changing the pace and course of agricultural research in the future all the way to a possible new method for fighting the AIDS virus HIV.

"The CRISPR-Cas9 system has already breached boundaries and made genetic engineering much more versatile, efficient and easy", Charpentier says. "There really does not seem to be a limit in the applications."

Explore further: RCas9: A programmable RNA editing tool

Viruses cannot only cause illnesses in humans, they also infect bacteria. Those protect themselves with a kind of 'immune system' which simply put consists of specific sequences in the genetic material ...

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Revolutionizing genome engineering: Review on history and future of the CRISPR-Cas9 system published

PORTLAND, Ore. -- Genetic engineering takes cells and alters their genes so they perform functions different from what nature originally intended. A new trend uses circuitry to re-engineer the cell. These biological circuits "wire" naturally occurring cells into a circuit that performs a new function, such as filling in for the dopamine-generating cells destroyed by Parkinson's disease.

"Our ultimate goal, many years from now, is complex medical applications, such as injection of a circuit into the bloodstream that looks for cancer cells and, when it finds one, injects a drug," Domitilla Del Vecchio, a professor at MIT, told EE Times. "Such a circuit would need a sensor, a computer, and an actuation component to inject the drug, and those are the kinds of components we are working on today."

Yeast cells (middle) are wired together like electronic components, but they communicate, not with electrical wires, but with chemicals that only plug into cells with the proper receptor. (Image: MIT)

Other possible applications include synthetic biological circuits that measure glucose levels constantly for diabetic patients and then automatically release insulin when it is needed.

The design process for such biocircuitry is slow and arduous compared with designing electronic circuits. For one thing, the researchers are not using nerves for communication. Instead, they use the normal communication method inside a natural cell, with the "output" secreting a chemical that only affects the "input" cells that have receptors tailored to be activated by that particular chemical.

The second big slowdown is the mathematics used to model the desired circuits. The researchers cannot use simple R-L-C equations like Ohm's Law. They must use the tedious mathematics of differential equations. "Biological circuits are very nonlinear, so we have to use differential equations to model them," Del Vecchio said.

Nevertheless, the payoff will make the effort worth it, since many maladies seem immune to solution by a simple symptom-treating drug. They require a complex cure that actively senses, computes, and responds. The best way to do that, according to MIT researchers, is to create cells that perform those functions internally, rather than trying to wire together an artificial neural network, as so many others have attempted.

Left to right: Ron Weiss, professor of biological engineering; Domitilla Del Vecchio, associate professor of mechanical engineering; and Deepak Mishra, MIT graduate student in biological engineering. (Image: MIT/Brian Teague)

"Besides nerve cells, there are many types of circuitry in biological systems, such as genetic circuitry that controls the expression of genes and the cells that controls the time keeping of the organism, such as when to get up in the morning," Del Vecchio said.

So far, most of the research group's circuits have been designed to sense something, using either yeast cells (in the illustration above) or bacteria cells. "Bacteria cells are much easier to work with, because they don't have a nucleus to deal with."

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Biologists Grow Living Circuits