Long-read DNA analysis can give rise to errors, experts warn

Phys.org | January 22, 2019

Advanced technologies that read long strings of DNA can produce flawed data that could affect genetic studies, research suggests. New methods that can read long sections of genetic material—categorised by a series of letters—are up to 99.8 percent accurate, however, in a genome of more than 3 billion letters, this may equate to millions of mistakes in the results. These errors may falsely indicate that an individual has a genetic difference that heightens their risk of a particular disease. Researchers say data produced by these technologies should be interpreted with caution, as it may create problems for analyzing genetic information from people and animals. Previously, genetic sequencing technologies were focused on reading short strings of DNA. These sequences would be patched together, which is time-consuming and labor-intensive.

Spotlight

The CRISPR-Cas9 system has revolutionized gene-editing, but cutting DNA isn’t all it can do. From turning gene expression on and off to fluorescently tagging particular sequences, this animation explores some of the exciting possibilities of CRISPR.

Spotlight

The CRISPR-Cas9 system has revolutionized gene-editing, but cutting DNA isn’t all it can do. From turning gene expression on and off to fluorescently tagging particular sequences, this animation explores some of the exciting possibilities of CRISPR.

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INDUSTRIAL IMPACT

Applied DNA Announces Receipt of Largest Single Purchase Order for LinearDNA™ To-Date

Applied DNA Sciences | October 11, 2022

Applied DNA Sciences, Inc. a leader in PCR-based DNA technologies, announced that it received its largest single purchase order for LinearDNA™ valued above the mid-six-figures. The order was placed under a long-standing supply agreement for the bulk manufacture of LinearDNA for a global manufacturer of in vitro diagnostics. Under the terms of the repeat order, the Company will deliver quantities of LinearDNA to the customer in the current quarter, with the full order expected to be fulfilled over the subsequent three quarters. LinearDNA is produced using an enzymatic manufacturing platform that eliminates the use of fermenters and bacteria required by plasmid DNA, the industry’s current manufacturing standard for DNA. LinearDNA eliminates many of the challenges associated with current plasmid-based DNA manufacturing and produces a DNA product without the risks of bacterial contamination and non-target DNA sequences. The enzymatic process provides the means to optimize a customer-specific chemistry and sequence of LinearDNA. This capability has been leveraged for diagnostic applications, including today's announced repeat order, and is commonly used when customers order LinearDNA for use as IVT templates for RNA production. “The application of DNA-based probes in molecular diagnostics is rapidly expanding to give the industry powerful new tools to enhance the diagnosis of infectious diseases, genetic disorders, and malignancies. Our proprietary enzymatic approach to manufacturing DNA via PCR underpins our ability to produce DNA more efficiently and rapidly relative to other DNA production methods and at scale. Applying this capacity also to the manufacture of therapeutic DNA for the next generation of genetic medicines, we believe LinearDNA sits at the intersection of two growing life sciences segments that hold the potential to transform human health.” Dr. James A. Hayward, president and CEO of Applied DNA About Applied DNA Sciences Applied DNA Sciences is a biotechnology company developing technologies to produce and detect deoxyribonucleic acid . Using PCR to enable both the production and detection of DNA, we operate in three primary business markets: (i) the manufacture of DNA for use in nucleic acid-based therapeutics; (ii) the detection of DNA in molecular diagnostics testing services; and (iii) the manufacture and detection of DNA for industrial supply chain security services. The Company’s common stock is listed on NASDAQ under the ticker symbol ‘APDN,’ and its publicly traded warrants are listed on OTC under the ticker symbol ‘APPDW.’

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INDUSTRIAL IMPACT

Ginkgo Bioworks Completes Acquisition of Zymergen

Ginkgo Bioworks | October 20, 2022

Today, Ginkgo Bioworks the leading horizontal platform for cell programming, and Zymergen announced that Ginkgo has completed its previously announced acquisition of Zymergen. The acquisition is expected to significantly enhance Ginkgo's platform by integrating strong automation and software capabilities as well as a wealth of experience across diverse biological engineering approaches. "Today marks an important step in our long-term growth as we complete the Zymergen acquisition and welcome their world-class team to Ginkgo. We are excited to integrate Zymergen's capabilities into our platform and explore new and expanded partnerships and opportunities for their diverse array of product concepts currently under development." Jason Kelly, CEO and co-founder of Ginkgo Bioworks Under the terms of the merger agreement entered into on July 24, 2022, Zymergen stockholders received, for each share of Zymergen common stock, 0.9179 shares of Ginkgo Class A common stock. Zymergen shares will no longer be traded on Nasdaq. Ginkgo Class A common stock will continue to trade on NYSE under the ticker symbol DNA. About Ginkgo Bioworks Ginkgo is building a platform to enable customers to program cells as easily as we can program computers. The company's platform is enabling biotechnology applications across diverse markets, from food and agriculture to industrial chemicals to pharmaceuticals. Ginkgo has also actively supported a number of COVID-19 response efforts, including K-12 pooled testing, vaccine manufacturing optimization and therapeutics discovery. About Zymergen Zymergen is a biotech company that designs and produces molecules, microbes and materials for diverse end markets. Zymergen partners with nature to make better products, a better way, for a better world.

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CELL AND GENE THERAPY

GenScript and Gladstone-UCSF Institute of Genomic Immunology Collaborate on Groundbreaking Non-Viral Cell Therapy Study

Genscript Biotech Corporation | September 23, 2022

GenScript USA Inc., the world's leading life-science research tools and services provider, is collaborating with researchers at the Gladstone-UCSF Institute of Genomic Immunology to advance the development of new, non-viral cell therapies that modify genomic sequences in the pursuit of more effective cell therapy products while limiting the cellular toxicity that is typically associated with previously available methods. A new study, published in Nature Biotechnology, details methods for achieving highly efficient non-viral knock-in using GenScript's GenExact™ single-strand DNA modified with Cas9-target sequences. This method achieved up to ˜40% knock-in efficiency in primary immune cell types. One powerful application of CRISPR/Cas genome editing technology involves the precise insertion of DNA sequences via the HDR pathway. Traditionally, researchers have relied on viral vectors to deliver DNA insertion templates used for gene therapy into cells. However, difficulties manufacturing large amounts of clinical-grade viral vectors have delayed getting cell therapies to patients. Additionally, viral vectors can insert genes at any location within the genome, leading to safety concerns. Previous research by the group at Gladstone and UCSF has shown that synthetic DNA templates can be delivered without the use of viral vectors, but high levels of double-stranded DNA can be toxic to cells, resulting in low efficiency. Efficiency can be improved using a modified version of the DNA templates that can bind to the Cas9 enzyme. However, additional work was required to improve the yield of successfully engineered cells and to make the process compatible with the manufacturing of future cell therapies. Those goals motivated the team's current study. In this study, the team tested modified GenExact ssDNA designed with Cas9-targeted sequences to determine if the gene-editing efficiency could be improved with lower toxicity. First, synthetic sgRNA was complexed with Cas9 protein to form a RNP complex. Then the RNP and ssDNA template were delivered into the cell via electroporation, enabling efficient gene editing. The team discovered that this combination of GenExact ssDNA with Cas9-targeted sequence offers up to 40% knock-in editing efficiency with minimal cellular toxicity. This approach can accelerate the development and manufacture of novel, high-yield non-viral gene therapies — and at lower cost. "We are very proud to have collaborated on this groundbreaking scale-up work by the talented team at Gladstone and UCSF. GenScript is excited for the opportunities that this high-yield cell-line engineering process will provide to our customers," said Ray Chen, Ph.D, president of GenScript Life Science Group. "We were very happy to partner with Genscript on critical experiments demonstrating high efficiency and yield of CAR knock-in cells at clinical scale. The long ssDNA produced by Genscript exceeded our expectations and helped us clearly demonstrate the potential for future therapeutic applications using these methods.", Brian Shy, MD, PhD, a former clinical fellow in the lab of Alex Marson, MD, PhD, director of the Gladstone-UCSF Institute of Genomic Immunology About GenScript Biotech Corporation GenScript Biotech Corporation is a global biotechnology group. Based on its leading gene synthesis technology, GenScript has developed four major platforms including the global cell therapy platform, the biologics contract development and manufacturing organization platform, the contract research organization platform, and the industrial synthesis product platform. GenScript was founded in New Jersey, USA in 2002 and listed on the Hong Kong Stock Exchange in 2015. GenScript's business operation spans over 100 countries and regions worldwide, with legal entities located in the USA, mainland China, Hong Kong, Japan, Singapore, the Netherlands, and Ireland. GenScript has provided premium, convenient, and reliable products and services for over 100,000 customers.

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