September 1, 2017 (Vol. 37, No. 15)

Industry Watch: 11 Organizations Urge Caution, Not Ban, on CRISPR Germline Genome Editing

Eleven genetics-focused professional organizations are urging researchers to use caution in applying human germline genome editing.

Stopping short of advocating a ban, they said future clinical applications should not proceed without at least a “compelling” medical rationale, a base of evidence that justifies clinical use, an ethical justification, and the solicitation and incorporation of stakeholder input through a “transparent public process.”

“Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing,” the organizations declared.

They also declared it “inappropriate” to use germline genome editing that would result in human pregnancy—yet urged against efforts to prohibit public funding of research.

“Human Germline Genome Editing,” was published August 3, 2017 in The American Journal of Human Genetics. The journal is owned and controlled by the American Society of Human Genetics (ASHG), one of the 11 organizations that crafted the policy statement.

The statement was issued a day after publication of a paper in Nature titled, “Correction of a Pathogenic Gene Mutation in Human Embryos.” The landmark study detailed the first-in-U.S. use of CRISPR to repair a germline mutation in human embryos created through in vitro fertilization.

Researchers from Oregon Health and Science University (OHSU), the Salk Institute for Biological Studies, and South Korea’s Institute for Basic Science—led by Shoukhrat Mitalipov, Ph.D., of the Center for Embryonic Cell and Gene Therapy at OHSU—carried out the study. It showed that modifying single-gene defects using the gene-editing technology CRISPR (clustered regularly interspaced short palindromic repeats) has the potential to be safe and accurate enough to use in human embryos.

Groups joining ASHG in issuing its statement included the Association of Genetic Nurses and Counsellors, the Canadian Association of Genetic Counsellors, the International Genetic Epidemiology Society, the National Society of Genetic Counselors, the American Society for Reproductive Medicine, the Asia Pacific Society of Human Genetics, the British Society for Genetic Medicine, the Human Genetics Society of Australasia, the Professional Society of Genetic Counselors in Asia, and the Southern African Society for Human Genetics.


Discovery & Development: Press the Gas, Release the Brake, Run Over Cancer

Not only are cancer immunotherapy approaches proliferating, they are being combined with traditional cancer therapies—and even with each other. One especially synergistic combination of immunotherapies would incorporate a checkpoint inhibitor—to “take the brakes off” the T-cell response to cancer cells—as well as an anticancer vaccine—to prime T cells against cancer-specific antigens and (potentially) enhance T-cell infiltration of the tumor microenvironment.

This combination approach was proposed a few years ago by scientists based at Johns Hopkins University and the National Cancer Institute (NCI). Since then, it has been supported by mathematical modeling, preclinical work, and Phase I clinical trials.

Modeling conducted by biological mathematicians at Renmin University of China and Ohio State University showed how a cancer vaccine, GM–CSF-secreting cancer vaccine, and a checkpoint inhibitor, an anti-PD-1 drug, could enhance each other’s effects. Details of the modelers’ work, which included suggestions on checkpoint/vaccine dose ratios, appeared last in May 2017 in an article in PLOS One. “The vaccine increases the number of tumor-infiltrating effector T cells,” the article’s authors wrote, “and the anti-PD-1 ensures that these cells remain active.”

More recently, Generex Biotechnology offered a summary of the progress its subsidiary, Antigen Express, has been making with the Ii-Key Hybrid Vaccine Platform. The summary makes note of Antigen Express’ collaboration with Merck, a joint evaluation of Antigen Express’ AE37 cancer vaccine in combination with Merck’s anti-PD-1 therapy, Keytruda® (pembrolizumab), in patients with metastatic triple-negative breast cancer. The evaluation, a Phase II clinical trial, was announced in July 2017.

The Ii-Key peptide binds allosterically to a region adjacent to the MHC Class II antigen binding domain. This interaction, which displaces existing resident antigens while anchoring the linked target antigen securely within the antigen-binding domain, allows the Ii-Key hybrid to “hijack” MHC Class II molecules. According to Antigen Express, preclinical and Phase I data currently support the use of Ii-Key hybrid vaccines in breast cancer, prostate cancer, cervical cancer, melanoma, HIV, swine flu, and diabetes.

Antigen Express adds that the top 50 cancer antigens listed by the NCI represent new Ii-Key hybrid vaccines. Besides inducing a heightened immunologic response, Ii-Key hybrid vaccines, Antigen Express insists, can be used to activate an alternative T-cell pathway, inducing immune tolerance to antigens, such as those implicated in autoimmune disease, allergy, and transplant rejection.


Genomics & Proteomics: Clinical Whole-Genome Sequencing Expands PerkinElmer Services

Providing continued solutions for genomic testing laboratories lies at the center of newly extended
services recently announced by PerkinElmer. The launch of PerkinElmer Genetics’ clinical genomics services—through integrated laboratories in the U.S., India, and China—will provide a global genomic lab-testing platform that performs screening and diagnostic testing, specializing in newborns and high-throughput next-generation sequencing for rare inherited diseases.

“We are pleased to extend our portfolio to include clinical whole-genome sequencing (WGS), which
expands the continuum of care from preconception to newborns. This offering will provide clinicians insights into the complex nature of rare and inherited diseases,” remarked Madhuri Hegde, Ph.D., vice president and CSO for laboratory services of PerkinElmer’s Diagnostics business group. “Because sequencing is not a standalone option, our ability to use dried blood spot samples and assimilate molecular and biochemical data from our global laboratories will improve interpretation of genomic variants.” 

The affordable whole-exome sequencing (WES) and WGS services announced by PerkinElmer are also offered in combination with biochemical profiling targeted for rapid WES and WGS for genetic disease diagnosis. While initially focused on newborn and ViaCord customers, PerkinElmer Genetics has also developed a biochemical and molecular testing menu to meet the needs of other segments, such as pharmaceutical companies and the markets it serves in China and India.

PerkinElmer Genetics currently has two CLIA-certified clinical laboratories based in Pittsburgh, PA and Branford, CT that process more than 500,000 samples a year. Their testing menus include newborn screening, biochemical profiling, second-tier molecular confirmatory testing, Sanger and NGS-based panels, and exome and genome sequencing. The addition of these new services could provide significant impact on the growing knowledge base surrounding rare genetic diseases, a currently underserved research field. 


Molecular Diagnostics: Fluidigm, Ascendas Genomics to Partner on MDx Systems and Assays in China

Ascendas Genomics will develop and commercialize molecular diagnostic systems and assays in China using Fluidigm’s Biomark™ HD and Juno™ microfluidic technologies, the companies said. Fluidigm’s microfluidic technology is designed to detect somatic and genomic variations from patient samples. The company says its technology is intended to enable highly scalable and automated workflows for quantitative PCR, gene expression, copy number variation analysis and next-generation sequencing library preparation.

The Biomark™ HD system is designed to enable users to run entire projects, from research to validation to routine screening, on a single system that combines digital PCR with simultaneous real-time data for counting and validation. Fluidigm says Biomark HD is flexible yet consistent, offering reliable production-scale throughput and single-cell sensitivity, with a wide variety of sample types and chemistry choices for most genomic applications.

The Juno Targeted DNA Sequencing Library Preparation System, which includes Targeted DNA Seq Library Preparation reagents, is intended to let users produce dozens to hundreds of sample libraries daily, with each sample enriched for up to 4,800 specific amplicons covering user-defined genes or genomic loci.

According to Fluidigm, Juno is optimized for use with Illumina® sequencing systems in combination with Fluidigm-supplied sample barcodes, allowing for accurate sequencing of more samples that is faster and more affordable than ever. Juno also serves as a universal controller to prepare integrated fluidic circuits for both gene expression and genotyping analysis when used together with Biomark HD.

“The Juno and Biomark HD systems demonstrate superior performance in automation and ease of use, and provide great potential to advance diagnostic testing for the clinical labs and hospitals in China to enable the future of precision medicine,” Ascendas Chairman and CEO Chengyong Yang, Ph.D., said in a statement.

Based in Zhongshan, China, Ascendas was established in 2014 and focuses on developing and applying genetic diagnosis-related products, especially newborn screening and oncology genetic tests.

Ascendas develops genetic solutions for diagnostic markets, and provides technical and consulting services to clinical research laboratories, academic institutions and biotechnology companies. The company also offers immunodiagnostic and molecular diagnostic tests to hospitals and health care centers through its subsidiary company, Ruikang Diagnostics, a commercial reference lab. 

“We strongly believe our partnership with Fluidigm will make it possible to develop cost-effective and robust genetic diagnostic tests for more patients in China,” Dr. Yang added.

As a result, Fluidigm reasons, the partnership with Ascendas will help it expand its presence in the world’s most populous nation. “We are very pleased to partner with Ascendas Genomics to expand our market position in China,” added Fluidigm President and CEO Chris Linthwaite.

The strategic partnership, whose value was not disclosed, will expand Fluidigm’s presence in China, where the company saw its revenue drop to $2.4 million in Q1, down 27% from $3.3 million in Q1 2016. China’s share of total Fluidigm revenue fell from 11% to 10%, according to the company’s Form 10-Q filing for the first quarter.

The China decline helped lower Fluidigm’s total Q1 Asia-Pacific sales 17%, to $4.987 million from $6.008 million a year ago.

China sales “benefited in the year-ago period from multiple genomics instruments sold into applied
customers adopting our technology for genetic testing,” Fluidigm CFO Vikram Jog told analysts on the company’s quarterly conference call, according to a transcript by Seeking Alpha.

During 2016, China sales nearly doubled, rising to $11.1 million—up $5.5 million or 97% from 2015. That surge brought total Asia-Pacific sales 18% above 2015, to $18.478 million, offsetting a reduction of sales in the rest of the region, primarily Japan.




























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