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NIH, Biotech Partner on Electro-Aided Crispr for Sickle Cell

Sickle cell illustration

Sickle cell illustration (National Heart, Lung, and Blood Institute)

11 June 2018. The National Heart, Lung, and Blood Institute and a biotechnology company are testing genome editing with electronically treated cells as a therapy for sickle cell disease. The arrangement between MaxCyte Inc. in Gaithersburg, Maryland and NHLBI, part of National Institutes of Health, involves sharing of the agency’s facilities and expertise, with no direct payment of funds.

MaxCyte offers a technology called flow electroporation exposing cells to an electrical field that the company says makes the treated cells more susceptible to transfection, including the addition of nucleic acids, such as DNA or RNA. In this case, flow electroporation is used with the genome editing technique known as Crispr, short for clustered, regularly interspaced short palindromic repeats, to correct mutations in genes producing hemoglobin, responsible for sickle cell disease.

Crispr harnesses bacterial defense mechanisms that use RNA to identify and monitor precise locations in DNA. The actual editing is done most often by the Crispr-associated protein 9, or Cas9, enzyme that programs RNA to silence genes and provide immunity against invading genetic material.

Sickle cell disease is a genetic blood disorder affecting hemoglobin, a protein in blood that delivers oxygen to cells in the body. People with sickle cell disease have hemoglobin molecules that cause blood cells to form into an atypical crescent or sickle shape. That abnormal shape causes the blood cells to break down, lose flexibility, and accumulate in tiny capillaries, leading to anemia and periodic painful episodes. Sickle cell disease is prevalent worldwide, and affects 70,000 to 80,000 people in the U.S., including about 1 in 500 people of African descent.

The company says its flow electroporation process makes possible transfection with more than 80 different types of cells with an efficiency exceeding 90 percent. For this project, MaxCyte is providing messenger RNA, or mRNA, molecules to help develop an efficient process for delivering corrected hemoglobin genes, as well as correct mutations in non-mutated cells that may contribute to the disease. NHLBI is expected to carry out safety and effectiveness tests with MaxCyte’s mRNA molecules in preclinical models of sickle cell disease.

The deal between MaxCyte and NHLBI is called a cooperative research and development agreement, or Crada. A Crada a collaborative project where agencies or national labs make their staff, facilities, and equipment available for research with a private company that also provides funding for the project, as well as its own staff, facilities, and equipment. Crada agreements often include provisions for licensing the results of the joint research, but no intellectual property aspects of this agreement were disclosed.

This is the second such agreement between an NIH institute and MaxCyte. As reported in Science & Enterprise in January 2017, MaxCyte and National Institute of Allergy and Infectious Diseases collaborated on using flow electroporation with Crispr-Cas9 to repair a genetic blood disorder known as X-linked chronic granulomatous disease, an inherited condition where phagocytes, white blood cells in the immune system, do not produce the proteins that protect against invading pathogens, such as bacteria and fungi.

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Single Technology Produces Vaccines for Multiple Infectious Diseases

Ebola diagnostics

Conducting Ebola diagnostics in the field (John Saindon, CDC.gov)

11 June 2018. A single technology platform is being used to design and produce vaccines that in tests with lab animals protect against a number of infectious diseases. A team from the company GeoVax Labs Inc. in Smyrna, Georgia reported their findings yesterday at a meeting of American Society for Microbiology in Atlanta.

Researchers from GeoVax Labs discussed results of proof-of-concept tests for vaccines designed to protect against Ebola, Zika, and Lassa fever — three different families of infectious diseases — with the company’s technology platform. That platform known as modified vaccinia Ankara, or MVA, delivers DNA or viruses, engineered to be benign, but still producing virus-like particles in the recipient. The virus-like particles are sufficiently similar to the real viruses to invoke an immune response in both antibodies and T-cells, but not cause the disease. GeoVax says the technology can also be used with vaccines against enveloped viruses, such as Ebola and Lassa fever, where the virus-like particles include pieces of the membranes surrounding the antigen proteins, to produce suitable immune responses.

The company tested vaccines designed to protect against each of the three diseases. The Ebola outbreak in 2014-15 caused a serious public health emergency in West Africa, with nearly 29,000 cases reported in Liberia, Sierra Leone, and Guinea, leading to more than 11,000 deaths. Democratic Republic of the Congo is facing another Ebola outbreak this year. Zika is a continuing public health problem in Mexico, Central and South America, and Africa. Lassa fever is spread most often by person-to-person contact, with outbreaks currently reported in Nigeria.

The GeoVax team injected single vaccine doses in lab animals, followed by challenge injections of the disease-causing microbes. For the Zika vaccine, a single dose of the company’s vaccine protected all of the mice against the disease-causing virus injected into the animals’ brains. Similar mice without the vaccine lost weight and died within a week. The Lassa fever vaccine also protected test mice against challenge disease injections into the brain. The researchers tested the Ebola vaccine with guinea pigs, hamsters, and rhesus monkeys, all of whom were protected against challenge disease injections.

“These data demonstrate a broad utility of the platform especially for development of single-dose vaccines against infectious diseases suited to combat epidemic in resource constrained countries,” says Farshad Guirakhoo, GeoVax’s chief scientist in a company statement. GeoVax says the vaccines are stable when refrigerated, but can also be freeze-dried for settings where constant refrigeration is not available. And its vaccines, says the company, can also be scaled-up and produced quickly to respond to epidemics.

GeoVax’s lead product is a preventive vaccine to protect against HIV infections, now in intermediate-stage clinical trials. The company is also developing therapeutic vaccines for HIV, currently in preclinical tests. In addition to Ebola. Zika, and Lassa fever vaccines, GeoVax is developing preventive vaccines for Marburg, Sudan, malaria, and HPV viruses, as well as therapeutic vaccines for hepatitis-B and tumor-associated antigen cancer. The company’s work on Zika, Lassa fever, and HIV is funded by grants from National Institute of Allergy and Infectious Diseases, part of National Institutes of Health.

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Five Essential Ways of Promoting Your Business

– Contributed content –

11 June 2018. The best way of making sure your company is successful going forward is to make sure you promote effectively. The good thing about running a business these days is that there are so many ways you can market your business as effectively as possible. You need to make sure you come up with the best means of promotion you can, and that sometimes means diversifying.

So, if you are serious about getting the best outcome for the company you need to make sure you are using the best possible methods of promotion. Think about how you can promote and advertise the brand effectively, and what is involved in helping the company grow. Do as much as you can to make sure you utilize these five excellent forms of business marketing right now.

Signage

Store signs

(Flickr)

It might seem outdated to you, but it is also important to try to make sure you embrace some of the classics. There are plenty of old-school marketing methods out there that will yield some really excellent gains for you as a business owner. One of the best in this category is signage, and it remains powerful to this day. You need to make sure you have some externally to promote the business. But, you also need to think about getting some drop ceiling clips and hang some signs in your store or office as well. Making sure you have great signage is so important for helping draw more attention to the company.

Business cards

Business cards

(Flickr)

Don’t knock them until you’ve tried them. Business cards are one of the most important and underrated forms of business marketing, and they are perfect for networking effectively with others. Get a set of business cards designed so you can showcase the company in a smart and professional manner. These can actually have a really huge bearing on the way your brand comes across to potential customers.

Email

Email newsletter graphic

(DBayIT.tech)

Email marketing has been around since the internet yet it is still one of the most important and effective forms of business marketing. Think about what you need to do to craft the perfect email, and whether you want to go for group email or individual email. There is a lot to consider in this respect, and it is important that you figure out the best style of approach to take when it actually comes to email marketing.

Web site

Web site on monitor

(.twimg.com)

Never overlook the importance of having an amazing web site in your business marketing arsenal. There are a lot of companies out there that don’t bother to work on perfecting their web site, but this is something that can be so effective. If you seriously want to perfect your marketing strategies like a pro, you need to be sure you focus on providing the best possible website to help your customers take to your business more.

Social media

Social media graphic

(Flickr)

No modern business is going to get very far without the use of social media. When it comes to promoting and advertising a modern brand, it is clear that social media is King. So, you might want to consider hiring a digital marketing team that will help you to spearhead the perfect social media marketing operation. This is going to have a huge bearing on the rest of the business moving forward so make sure you don’t overlook it.

These five ideas represent some of the best ways of promoting and marketing a brand you can think of. There is a lot to consider in this respect, and it is important that you do what is best for the company in the long run. That means focusing on helping to market and advertise the brand as best you can.

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Infographic – Cloning Gains More U.S. Support

Acceptability of cloning

Click on chart for full-size view (Statista)

10 June 2018. Genomics is a major story we follow at Science & Enterprise, but we do not often report on moral or ethical concerns surrounding research on the genome, either in animals or humans. Thus, we’re indebted to our friends at Statista who published a chart this week showing that the American public increasing supports the idea of genetic cloning, and this weekend’s infographic.

Although still a minority, about 4 in 10 of those polled by the Gallup organization in May of 2018 say they find the cloning of animals morally acceptable, a marked increase from 2010 and 2002, when about 3 in 10 believed cloning of animals was acceptable. But also in 2018, a majority (57%) of Americans still finds cloning animals morally wrong. In addition, cloning of humans is deemed acceptable today by a only small percentage of Americans, 16 percent, and that’s about double the 7 percent recorded in 2002.

Regular editorial posting on Science & Enterprise resumes tomorrow.

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Top Ways that Technology Could Boost Your Small Business

– Contributed content –

Analytics charts

(Lukas, Pexels.com)

8 June 2018. When you operate a small business, you probably have to think about the technology that you have, the upgrades that are available and even your budget as well. This can be difficult if you have no idea what is out there, but there are things that you can do to help yourself turn all of this around. If you want to find out more then take a look below.

Understanding your customer base

If you have a store then you will want to place your products in such a way that they get noticed. The problem that a lot of people have is that they have no idea how to do this, but by using data from an analytics system, you can be sure to find out everything you need to know. Strategic product placement is crucial to your sales and it also gives you the chance to utilise your retail store for profit as well. When you have a system like this, you can easily use video to map out any customer movements that happen in your store and this also gives you the chance to identify your own hot spots. This can work wonders for your sales and you would be surprised at how much this can help you to really build a profile for the different customers that you have.

If you don’t have a system like this then the whole thing will be done on guesswork and this isn’t going to help you out at all. When you have a tech software that is able to handle your video-based data, you can easily track the traffic at regular intervals and this can help you to plan out your staff rota as well so you know that you won’t have any problems there.

Managing your mobile workforce

Do you sometimes wish that you could split yourself into many different pieces so that you can see all of your workers at the same time? Don’t worry, you are not alone, there are so many people who wish that they could do this every single day, and even though you might not be able to do this, it is possible for you to try and make sure that your employees are showing up on time. Technology gives you the chance to monitor your current headcount at every location that you have. If you are a staff member short then you will be sent an urgent request and this gives you the chance to move your staff around so that they can fulfill any needs that you have. It is even possible for you to get an application that can be combined with this as well, and this is great when the time does come for you to organize your payroll.

When you integrate technology like this, you will easily be able to avoid overpaying employees who aren’t actually showing up and it can provide you with the valuable insight you need to stop any problems from happening in the future. If you are looking to upgrade your business technology then it may be worth you looking into various data center tier ratings, so that you can get the best result out of your technology across the board.

Woman with laptop

(Bruce Mars, Pexels.com)

Selling points

If you have one point of sale in a fast food restaurant then this will keep a lot of customers waiting. It also limits the amount of sales that you can make per day as well. If you are able to integrate a self-service station however then this means that your customers can serve themselves and it also means that they can checkout on their own. The best thing about this is that you can still use their data to find out which items are selling the best and you can even add a bunch of new features as well. You can integrate a point-based scheme and this means that if you ever want to reward your customers, you can.

By upgrading your technology, you can also benefit by tracking your current inventory and if you ever run out of a product, you will get notified. Nothing can quite compare to the convenience that this has to offer and when you go to the right developer, you will be able to integrate all of this with ease. Not only will this help to take your business to that next level, but it will also help you to really stay on top of things.

Your delivery

If you make deliveries yourself to your customers then you will know what a convenient way this is to try and save money. You can make the most out of your technology by installing a system that will show you the fastest route to a stop. This will save you time, money and even manpower as well. When you have these types of tools at your disposal, you can effectively minimise the amount that you have to invest in your fleet and you can also capture data that will help you to predict any wet or dangerous driving conditions. This will help you to avoid disasters and accidents, not to mention that it will also help to make your deliveries much more efficient as well.

Automatic invoicing

Do you sell products online? Then you will know how hard it can be to really stay on top of everything, you will also know how hard it can be to remind customers when they need to pay as well. if you want to get around all of this then you can easily set up automatic invoicing. This will prompt your customers when it is time for them to pay and it will also try and take the payment automatically as well. This is a great way for you to boost the amount of profit that you can make and it will also make it way easier for you to really provide your customers with the service that they need. Automatic invoicing is essential when you have a small business, and it won’t cost half as much when compared to having a fully devoted accountant working with you.

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Making Your Own Beer From Home

– Contributed content –

Pouring beer

(Rawpixel, Pexels.com)

7 June 2018. When it comes to scientific experiments, what kind is better than the one that gives you alcohol at the end? You have probably heard about people trying out beer-brewing their own home before, in all likelihood with rather mixed results. As it happens, it is one of those things which is at once simple and complex, in that the process itself is not too full-on, but it can take a long time to master it and end up with great beer. In this article, we are going to go through the basic process of making your own beer, so that you can give it a go yourself and see what happens. If nothing else, there are worst experiments to fail.

Gather your equipment

You will need a number of things for this, ranging from a sinobatoo mini-keg to a large container to mix all the ingredients in and get brewing in the first place. On top of that, you will also need the ingredients for the beer itself, which includes malt grains or liquid, hops, whatever other special grains you want to add for flavor, and yeast. All of these are easy to find online, and you can even get some of them – like yeast and grains – in a number of supermarkets and other high street shops. Once you have gathered everything you are going to need, you can get to work on the actual brewing process itself.

Steep grains

Once you have gathered and cleaned all of your equipment, it is time to steep your grains. This is basically a matter of putting your speciality grains into a grain bag, which is essentially a mesh bag, and steep them in a large pot in hot water for around half an hour. Steeping in this way allow the flavor to come out more fully, so the more patient you are, the better. Then you will need to drain the bag and extract the grains.

Add malt

Next, you need to grab your malt extract and add it to the mixture, taking care as you bring the whole thing to the boil. You will be adding the hops at various intervals in order to introduce different kinds of taste and texture to the beer, bearing in mind that those added early produce bitterness and those added late produce more flavor and aroma. This is only a general rule, however, so it’s all about experimenting and seeing what works. Once you have done all of this, you are well on your way to creating your own delicious beer.

Chill & ferment

You then need to chill the entire mixture as quickly as possible, for example by using an ice bath. Once it is cool, you can then put it in your fermenter to ferment. It is now a matter of waiting to see what happens, and all of the hard work is pretty much done. Once you have fermented your bear, it is time to bottle it and drink – or share with your friends.

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Taking a Break

Oyster catchers

(A. Kotok)

4 June 2018. Science & Enterprise is taking an early summer break, and we will not be publishing any editorial posts for the rest of this week. While we may have contributed content during this time, our regular editorial posts will resume on Monday, 11 June.

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Bacterial Genome Recoded to Produce Stable Protein Drugs

E. coli bacteria

E. coli bacteria (Agricultural Research Service, USDA)

4 June 2018. A biotechnology lab devised techniques for genetically engineered bacteria to produce synthetic proteins that can last longer and are more stable than current protein production methods. Researchers from University of Texas in Austin describe their processes in today’s issue of the journal Nature Biotechnology (paid subscription required).

A team from the lab of biochemistry professor Andrew Ellington at UT-Austin is seeking reliable processes for producing synthetic biologic drugs that have longer shelf and activity lives than current protein-based drugs, such as insulin and monoclonal or highly targeted antibodies. Proteins are chains of amino acids, including cysteine, an amino acid that interacts with other compounds in the body’s cells and quickly breaks down the proteins in the drugs.

Adding the element selenium to cysteine, however, is known to strengthen and stabilize cysteine while maintaining the amino acid’s functions. The problem, say the researchers, is the lack of a reliable method for producing selenocysteines in sufficient quantities that work well in synthetic proteins. The solution proposed by Ellington and colleagues is to re-engineer the genomes of E. coli bacteria to create a synthetic strain of the bacteria that produces selenocysteines in place of natural cysteine amino acids. While E. coli bacteria are popularly associated with food poisoning, there are many benign strains of the microbe, which are well studied and often used as model organisms in biology labs.

To genetically engineer E. coli, the researchers used a beta-lactamase enzyme often associated with antibiotic-resistant bacteria but with a modified chemistry to bind selenium to cysteine. With this technique the team could create an E. coli strain that produces selenocysteines, but they also directed the evolution of this strain to dominate natural strains in an E. coli community. As a result, say the researchers, they developed a functioning E. coli strain that reliably produces selenocysteine proteins, and in unlimited quantities.

“We have adapted the bacteria’s natural process for inserting selenocysteine to remove all the limitations,” says postdoctoral researcher and first author Ross Thyer in a university statement, “allowing us to recode any position in any protein as a selenocysteine.” The team further engineered E. coli to express fluorescent proteins that illuminate, allowing the researchers to quantify production of selenocysteine proteins. They say the techniques make it possible for the engineered microbes to indefinitely produce selenocysteine proteins in industrial-scale quantities.

Ellington and Thyer are co-founders with Harvard University geneticist and serial entrepreneur George Church and others of the start-up enterprise GRO Biosciences in Cambridge, Massachusetts to produce synthetic proteins from genetically-recoded bacteria, and serve as scientific advisers to the company. In September 2017, GRO Biosciences secured seed capital of $2.1 million and announced plans to produce therapeutic proteins with expanded potency and stability. As reported by Science & Enterprise in August 2016, Church and colleagues from another company he founded pioneered techniques for streamlining the E. coli genome, removing redundant elements.

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Blood Tests Shown Able to Identify Early Lung Cancer

lung illustration

(Kai Stachowiak, Pixabay)

4 June 2018. Results from a large-scale clinical trial show an analysis of blood samples can detect and identify the presence of characteristic DNA indicating a person may have early stages of lung cancer. Findings from the study are scheduled for presentation today by a team from Dana-Farber Cancer Institute in Boston and Grail Inc. in Menlo Park, California that developed the test at the annual meeting of American Society of Clinical Oncology, or ASCO, in Chicago.

Lung cancers, both small cell and non-small cell, are the second most common type of cancer, accounting for 14 percent of all new cancer cases. Only breast cancer in women and prostate cancer in men have higher rate of occurrence. American Cancer Society estimates some 234,000 people in the U.S. will have lung cancer in 2018, leading to more than 154,000 deaths. The group says more people die from lung cancer than other forms of the disease for men and women, eclipsing deaths for colon, breast, and prostate cancers combined.

Grail Inc.’s technology tests blood samples for the presence of DNA circulating in the blood stream characteristic of tumors to detect, but also identify the type of cancer. Circulating tumor DNA, says the company, makes up only a small fraction of the DNA in blood, resulting in weak signals from tumor DNA, thus requiring intense analysis to separate these signals from background noise. Grail says it sequences DNA captured in blood generating a terabyte of data on each patient, with a deep level of analysis that includes machine learning to determine the type and severity as well as the presence of cancer.

The company is sponsoring a clinical trial enrolling some 15,000 participants to help develop and validate its technology. Of the 15,000 individuals in the trial, known as the Circulating Cell-Free Genome Atlas, 10,500 participants are cancer patients while the remaining 4,500 are a cancer-free comparison group. So far, about 12,000 participants are enrolled at 141 sites in the U.S. and Canada. All participants are providing blood samples, while cancer patients are also offering tissue samples from their tumors, with the individuals’ medical records  tracked annually for 5 years.

A team led by lung cancer specialist Geoffrey Oxnard at Dana-Farber Cancer Institute is providing one of the first reports from the trial at the ASCO meeting. The researchers focused on a subset of 1,627 participants divided about equally between newly diagnosed cancer patients and cancer-free individuals for comparison. Blood samples from participants were analyzed with 3 methods in development by Grail:

 – Targeted sequencing of 507 genes to find non-inherited mutations

 – Whole genome sequencing, also to detect non-inherited genomic variations

 – Whole genome sequencing, where DNA is first treated with sodium bisulfite to highlight  changes in the DNA caused by methylation, where the chemical structure of DNA is altered by disease or injury.

The researchers were looking particularly at the ability of the tests to identify the 127 known lung cancer patients in the sample, which ranged from an early-stage localized form of the disease to advanced cases where the cancer metastasizes or spreads to other parts of the body. The results show the targeted sequencing correctly identified the about half (51%) of the earlier stage cancers and the vast majority (89%) of late-stage cancer cases. Whole genome sequencing accurately characterized nearly as many (41%) of the earlier stage cancers and about the same percentage (87%) of the advanced stage disease cases as the targeted sequencing, with whole genome plus bisulfite sequencing returning similar identifications, 38 percent of early stage cases and 89 percent of late stage cancers.

While the findings show high accuracy rates for detecting and identifying cancer, the sequencing processes also found more than half (54%) of non-inherited mutations were caused by a non-cancerous white blood cell condition called clonal hematopoiesis of indeterminate potential. or CHIP, associated with aging. Nonetheless, the authors say the results are encouraging enough to continue development of the tests to provide better tools for early-stage lung cancer diagnosis, but also better accounting for CHIP conditions.

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Infographic – Immigrants Boost High-Value U.S. Start-Ups

Countries of immigrant start-ups

Origin of immigrant entrepreneurs starting new companies valued at $1 billion or more. Click on image for full-size view. (Statista)

2 June 2018. The Department of Homeland Security this week proposed ending the International Entrepreneur Rule that allows immigrant entrepreneurs to start new businesses in the U.S. The Trump administration’s crackdown on immigration, whether illegal or not, alarms our top universities where foreign-born researchers conduct much of their science, as we’ve reported in Science & Enterprise, and now that crackdown is being extended to people starting new businesses.

This weekend’s infographic, from our friends at Statista, shows the potential impact of this action. Based on data from 2016, about half — 44 of 87 — U.S. start-ups valued at $1 billion or more were founded by immigrants, with India providing the largest number of these entrepreneurs. The National Foundation for American Policy that prepared the report says each of these new enterprises creates some 760 jobs. While this issue may not have the emotional pull of other Trump immigration policies, it suggests factors other than good business sense are at work.

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