Cell Therapy News Volume 19.24 | Jul 16 2018

TOP STORY

Meganuclease Targeting of PCSK9 in Macaque Liver Leads to Stable Reduction in Serum Cholesterol

Scientists showed that single infusions in six non-human primates of adeno-associated virus vector expressing an engineered meganuclease targeting PCSK9 results in dose-dependent disruption of PCSK9 in liver, as well as a stable reduction in circulating PCSK9 and serum cholesterol. [Nat Biotechnol] Abstract | Press Release

(Ranked by impact factor of the journal)

Fetal Gene Therapy for Neurodegenerative Disease of Infants

Fetal intracranial injection of adeno-associated virus vector reconstituted neuronal glucocerebrosidase expression. Mice lived for up to at least 18 weeks, were fertile and fully mobile. [Nat Med] Abstract

CRISPR-Enhanced Engineering of Therapy-Sensitive Cancer Cells for Self-Targeting of Primary and Metastatic Tumors

Safe elimination of therapeutic cancer cells after treatment was achieved by co-engineering with a prodrug-converting suicide system, which also allowed for real-time in vivo positron emission tomography imaging of therapeutic tumor cell fate. [Sci Transl Med] Abstract

Clarin-1 Gene Transfer Rescues Auditory Synaptopathy in Model of Usher Syndrome

Cochlear gene therapy in vivo, through adeno-associated virus-mediated Clrn1 transfer into hair cells, prevented the synaptic defects and durably improved hearing in postnatal hair cell-specific conditional mice. [J Clin Invest] Full Article | Press Release

FGF21 Gene Therapy as Treatment for Obesity and Insulin Resistance

Adeno-associated viral vectors were used to genetically engineer liver, adipose tissue, or skeletal muscle to secrete FGF21. Treatment of animals under long-term high-fat diet feeding or of ob/ob mice resulted in marked reductions in body weight, adipose tissue hypertrophy and inflammation, hepatic steatosis, inflammation and fibrosis, and insulin resistance for > 1 year. [EMBO Mol Med] Full Article | Graphical Abstract

Autologous Adoptive T-Cell Therapy for Recurrent or Drug-Resistant Cytomegalovirus Complications in Solid Organ Transplant Patients: A Single-Arm Open-Label Phase I Clinical Trial

In this prospective study, 22 solid organ transplant recipients with recurrent or ganciclovir-resistant cytomegalovirus (CMV) infection were recruited and of these, 13 patients were treated with in vitro-expanded autologous CMV-specific T cells. [Clin Infect Dis] Abstract

Efficient Gene Transfer to the Central Nervous System by Single Stranded Anc80L65

Researchers compared the transduction efficacy of Anc80L65 with conventional adeno-associated vector (AAV)9 in the central nervous system after intravenous, intracerebroventricular or intraparenchymal injections. Anc80L65 was more potent at targeting the brain and spinal cord after intravenous injection than AAV9, and mostly transduced astrocytes and a wide range of neuronal subpopulations. [Mol Ther Methods Clin Dev] Abstract

Targeting the Root Cause by a Systemic scAAV9-hIDS Gene Delivery: Functional Correction and Reversal of Severe MPS II in Mice

Investigators developed a scAAV9-hIDS vector to deliver the human iduronate-2-sulfatase gene and test it in mouse model. They treated MPS II mice at different disease stages with an intravenous injection of scAAV9-mCMV-hIDS at different doses. [Mol Ther Methods Clin Dev] Abstract

Adenovirus Coding for Interleukin-2 and Tumor Necrosis Factor Alpha Replaces Lymphodepleting Chemotherapy in Adoptive T Cell Therapy

Immune cells responsive to tumor necrosis factor α interleukin-2 were studied using an immunocompetent mouse melanoma model infused with ovalbumin-specific T cells. [Mol Ther] Abstract

Enhancement of Chondrogenesis of Adipose-Derived Stem Cells in HA-PNIPAAm-CL Hydrogel for Cartilage Regeneration in Rabbits

The chondrogenic effects of hyaluronic acid (HA)-modified hydrogels on rabbit ADSCs (rADSCs) were confirmed in vivo by the intraarticular injection of hydrogel-embedded rADSC constructs into rabbit synovial cavities for three weeks and tracing with CM-DiI labeling. [Sci Rep] Full Article

More Expansive Gene Transfer to the Rat CNS: AAV PHP.EB Vector Dose-Response and Comparison to AAV PHP.B

Scientists characterized the relatively novel adeno-associated virus PHP.EB vector for expansive gene transfer in the CNS of adult rats at three doses. The dose-response data were consistent; expression levels can be controlled in a reproducible manner in the rat from moderate to robust levels. [Gene Ther] Abstract

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Urine-Derived Cells for Human Cell Therapy

The authors discuss the characteristics and therapeutic applications of urine-derived cells for human cell therapy. Conclusively, with detailed study and optimization, urine-derived cells have a prospective future to generate functional lineage-specific cells for patients from a clinical translation point of view. [Stem Cell Res Ther] Full Article

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Krystal Biotech to Present Update on KB103 Program for Treatment of Dystrophic Epidermolysis Bullosa

Krystal Biotech Inc. announced a presentation on the company’s lead product candidate, KB103, the first-ever topically-applied gene therapy being developed for the treatment of dystrophic epidermolysis bullosa. [Press release from Krystal Biotech Inc. discussing research to be presented at the 2018 debra Care Conference (DCC), Chandler] Press Release

MaxCyte Receives US FDA Investigational New Drug Clearance for First Clinical Program

MaxCyte announced that it has received Investigational New Drug clearance from the FDA to begin a clinical study in the United States with its first wholly-owned chimeric antigen receptor therapeutic candidate, MCY-M11. [MaxCyte, Inc.] Press Release

Axovant Announces Global Licensing Agreement for AXO-AAV-OPMD Program for Treatment of Oculopharyngeal Muscular Dystrophy and Broader Platform Collaboration with Benitec Biopharma

Axovant Sciences announced that it has licensed exclusive global rights to an investigational Silence-and-Replace gene therapy program from Benitec Biopharma for the treatment of oculopharyngeal muscular dystrophy (OPMD), and has also entered into a research collaboration for the development of five additional gene therapy products in neurological disorders. [Axovant Sciences, Inc.] Press Release

MedImmune and 4D Molecular Therapeutics Collaborate to Design, Develop and Commercialize AAV Gene Therapy for Chronic Lung Disease

MedImmune and 4D Molecular Therapeutics (4DMT) announced a collaboration to develop and commercialize a gene therapeutic for patients with chronic lung disease, utilizing 4DMT’s novel discovery platform to generate optimized AAV vectors. [MedImmune] Press Release

Transgene and Tasly Biopharmaceuticals Conclude Strategic Agreements for the Rights of Transgene’s Virus-Based Immunotherapies TG6002 and TG1050 in Greater China

Transgene signed a series of agreements with Tasly Biopharmaceuticals Co., Ltd. involving T601 and T101, two immunotherapeutics developed by the Transgene-Tasly joint venture in China. [Transgene] Press Release

Nohla Therapeutics Receives FDA Orphan Drug Designation for Dilanubicel for Hematopoietic Stem Cell Transplant Patients

Nohla Therapeutics announced that the FDA has granted Nohla’s lead product candidate, dilanubicel, Orphan Drug Designation for reduction of morbidity and mortality associated with hematopoietic stem cell transplant. [Nohla Therapeutics] Press Release

Pfizer Initiates Pivotal Phase III Program for Investigational Hemophilia B Gene Therapy

Pfizer Inc. and Spark Therapeutics announced that Pfizer initiated a Phase III open-label, multi-center, lead-in study (NCT03587116) to evaluate the efficacy and safety of current factor IX prophylaxis replacement therapy in the usual care setting. [Pfizer Inc.] Press Release

BioNTech and Genevant Sciences Sign Strategic mRNA-Focused Partnership in Rare Diseases

BioNTech AG and Genevant Sciences announced that they have entered into a collaboration to develop five mRNA therapeutic programs for rare diseases with high unmet medical need. The companies have also agreed a series of exclusive licenses covering the application of Genevant’s delivery technology to five of BioNTech’s oncology programs. [BioNTech AG] Press Release

Potential DNA Damage from CRISPR Has been ‘Seriously Underestimated,’ Study Finds

From the earliest days of the CRISPR-Cas9 era, scientists have known that the first step in how it edits genomes — snipping DNA — creates an unholy mess: Cellular repairmen frantically try to fix the cuts by throwing random chunks of DNA into the breach and deleting other random bits. Research suggests that’s only the tip of a Titanic-sized iceberg: CRISPR-Cas9 can cause significantly greater genetic havoc than experts thought, the study concludes, perhaps enough to threaten the health of patients who would one day receive CRISPR-based therapy. [STAT News] Editorial

Science Journals End Open-Access Trial with Gates Foundation

The publisher of Science ended a pilot partnership that allowed open-access (OA) publishing for researchers funded by the Bill & Melinda Gates Foundation. The trial was an effort to accommodate a policy clash between the Gates Foundation, which has enforced strict OA demands since 2017, and publishers that run subscription journals which don’t comply with those terms. [Nature News] Editorial

Researchers Celebrate Rejection of Controversial Copyright Policy

Early-career researchers are pleased at European leaders’ rejection of a copyright policy that would have introduced restrictions to text-and-data mining of scientific papers. [Chemistry World] Editorial

FDA

Statement from FDA Commissioner Scott Gottlieb, M.D. on Agency’s Efforts to Advance Development of Gene Therapies (FR Doc. No:PressAnnouncements) Notice

Human Gene Therapy for Hemophilia; Draft Guidance for Industry; Availability (FR Doc. No:2018-14875) Notice

Chemistry, Manufacturing, and Control Information for Human Gene Therapy Investigational New Drug Applications; Draft Guidance for Industry; Availability (FR Doc. No:2018-14866) Notice

Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus during Product Manufacture and Patient Follow-Up; Draft Guidance for Industry; Availability (FR Doc. No:2018-14868) Notice

Long Term Follow-Up after Administration of Human Gene Therapy Products; Draft Guidance for Industry; Availability (FR Doc. No:2018-14867) Notice

NEW 26^th European Orthopaedic Research Society (EORS) 2018
September 25-28, 2018
Galway, Ireland

Visit our events page to see a complete list of events in the community.

NEW Research Associate – Neuroimmunology (Thomas Jefferson University)

NEW Research Assistant or Associate – Cell Therapy (California Institute for Biomedical Research)

Scientia PhD – Gene Therapy (University of New South Wales)

Postdoctoral Fellow – DNA Damage Repair and Pediatric Sarcoma Therapy (University of Texas Health Science Center at San Antonio)

Postdoctoral Position – Corneal Diseases (University of California, Los Angeles)

PhD Student – Cellular Immunotherapy (Glycostem Therapeutics)

Research Associate/PhD Position – iPS Cell-Derived Neurons to Model Parkinson’s Disease (TU Dresden)

Postdoctoral Fellow – Cell and Gene Therapies for Cardiac Arrhythmias and Heart Failure (Duke University)

Postdoctoral Position – Human Pluripotent Stem Cell-Based Cell Therapy in Type 1 Diabetes (University of Copenhagen)

Scientist/Senior Scientist – Lentivirus Production (Obsidian Therapeutics)

Postdoctoral Fellow – Immunology, Immunotherapy, Gene Therapy (City of Hope)

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