Allele Publication Explains cGMP Generation of Induced Pluripotent Stem Cells

The discovery that adult somatic cells can be reprogrammed to pluripotent stem cells has given the biomedical community a powerful platform for personalized medicine. However, the translation of cell therapies from bench to bedside holds a significant challenge. Realizing the clinical potential for stem cells requires their production under current Good Manufacturing Practice (cGMP) regulations enforced by the FDA. A new protocol (http://onlinelibrary.wiley.com/doi/10.1002/cpsc.18/abstract) published by scientists at Allele and detailed in this quarter’s issue of Current Protocols in Stem Cell Biology, reveals key conditions required for converting adult fibroblasts to induced pluripotent stem cells (iPSCs) under cGMP regulations.¹

The patent-pending protocol is an update to a previous protocol that describes how to reprogram fibroblasts to iPSCs using mRNA. “The system of using mRNA to reprogram fibroblasts presents itself as a very favorable candidate for generating iPSCs for cell therapy” according to the senior author of the paper and CEO of Allele, Dr. Jiwu Wang, “our company is committed to developing stem cell based therapies using this protocol and through the establishment of our own stem cell GMP facilities here in California”. mRNA transfection is “footprint free”, meaning no insertions or alterations have been made to the genome. Transfection of mRNA is also “cleanup free,” because mRNA transcripts are supplied to the cells in the culture medium only for the time required to induce pluripotency. Furthermore, genomic analyses of iPSCs reprogrammed using mRNA indicate that this method of conversion is unlikely to introduce problematic mutations.²

The new version of the protocol describes reprogramming technology that utilizes all cGMP-certified reagents and vessels, meaning that every material is manufactured under guidelines that allow for ancillary use in manufacturing processes related to cell therapy. All materials described in the protocol – from cell medium and components to the coating for tissue culture plates – were meticulously evaluated at every step of generating and storing iPSCs. For truly cGMP produced cell lines, all processes should take place in certified cleanrooms with qualified equipment and thoroughly trained operators.

Establishing a cGMP process for any product intended for human use is a daunting undertaking. Unlike drugs and small-molecule pharmaceuticals, stem cells are living entities whose production cannot be chemically synthesized. Therefore, special considerations must be made – particularly for making individual cell lines – to help assure the highest safety and quality of downstream stem cell products. Adhering to cGMP regulations infuses high quality into the design and manufacturing process at every step. Through rigorous testing, researchers at Allele have identified critical parameters for generating iPSCs from fibroblasts that are cGMP-compliant, and are optimistic that the methods described in this recent publication will serve as a launch pad for the development of future cell products and therapies.

 

1. Ni Y, Zhao Y, Warren L, Higginbotham J, Wang J. cGMP Generation of Human Induced Pluripotent Stem Cells with Messenger RNA. Current Protocols in Stem Cell Biology,2016; 39:4A.6.1-4A.6.25.
2. Bhutani K, Nazor KL, Williams R, et al. Whole-genome mutational burden analysis of three pluripotency induction methods. Nature communications. 2016;7:10536.

Allele GMP CRO and Cell Therapy

Tags: Allele Therapeutics, CA company, CIRM, GMP, iPSC, stem cell therapy

Allele Biotechnology & Pharmaceuticals Forming Cell Banking Business for Personalized Medicine

Allele to Generate Human iPS Cells under Good Manufacturing Practice for Private Individuals for Potential Therapeutic Use and Future diagnostics; Cell Banking Scientific Advisory Board formed

October 06, 2015 11:25 AM Eastern Daylight Time
SAN DIEGO–(BUSINESS WIRE)–Allele Biotechnology & Pharmaceuticals, Inc. (“Allele”), a leader in the development of specialized cells for regenerative medicine and pharmaceutical drug discovery, today announced plans to form a commercial business for the banking of human induced pluripotent stem cells (iPSCs) by private individuals.

Allele is pleased to have Drs. Mahendra Rao and Joseph Paulauskis as the first members of its Scientific Advisory Board (SAB) for iPSC banking and cGMP production. Dr. Rao is a world-renowned scientist in the fields of stem cells and medicine, having served as the VP of Regenerative Medicine at Invitrogen, founding Director of the NIH Center for Regenerative Medicine, Chair of the Biological Response Modifiers Committee (BRMAC, now CTAGT) of the FDA, and he is currently Chief Strategy Officer at Q Therapeutics. Dr. Paulauskis is the Chief Operating Officer of Paradigm Dx as well as the Vice-President of Research and Biobanking for the International Genomics Consortium, and has previously held senior positions in pharmacogenomics at Pfizer. Allele plans to make additional appointments to the SAB as individuals with world-class experience and expertise are identified.

Human iPSCs are cells that can be grown to virtually infinite numbers and can become any cell in the human body, features which hold great promise for therapies that can alleviate or cure human disease. Allele’s business model recognizes that an individual can have their own cells ready for future therapeutic use via the generation and storage of iPSCs from that individual’s skin cells. While this is similar to what is done with newborn cord blood, iPSCs can be generated from humans of any age. The banking of human iPSCs for potential future therapeutic use is a relatively new industry with unprecedented potential, and Allele is benefitting from expert opinions internally and from current and future SAB members, ensuring a solid scientific and ethical foundation for this business.

In addition to serving its customers, Allele’s iPSC bank will be an unparalleled resource for biomedical research. Proper consent and privacy guardianship will allow thousands of iPSC lines with accompanying sequence database and health information to be made available from the bank to scientists and clinicians. Currently, iPSC banks are funded by government agencies at multi-million dollar costs per project; Allele’s model does not rely on tax dollars and provides potentially a larger bank of iPSCs of higher quality to aid research and treatment efforts. To this end, NIH Director Dr. Francis Collins recently announced the implementation of the Precision Medicine Initiative (PMI), the goal of which is for health care professionals to have the resources to take into account individual differences in genes, environments, and lifestyles that contribute to disease when providing treatments in the new era.

“We are happy to have the guidance from world leading experts in stem cells, biobanking, and cell therapy fields such as Drs. Rao and Paulauskis”, said Jiwu Wang Ph.D., President and CEO of Allele. “We believe that setting the bar high will be ultimately beneficial to future customers, fellow researchers, industry partners, and regulatory agencies alike. We are happy to see the recent release by the International Society for Stem Cell Research of a draft of ‘Guidelines for the Clinical Translation of Stem Cells’, whose principals we plan to follow closely. We also intend to obtain certification by the cord blood banking association AABB, if possible, and abide by other regulatory rules as they become public, such as the “Stem Cell Clinical Research Management (tentative)” by the Health Commission of China, if and when we move to operate under that jurisdiction”.

Towards the establishment of this business effort, Allele has recently purchased an 18,000 square-foot facility, located near its headquarters in San Diego, California. This new facility will be the center of cGMP-production of human iPSCs using Allele’s proprietary synthetic mRNA platform, a technology that generates cells with neither the random integration of foreign DNA nor the use of viruses or virus-based elements, drawbacks common to other technologies for making hiPSCs; thus, the “footprint-free” cells generated by Allele’s synthetic mRNA platform are optimally suited for therapeutic use, and Allele’s technology has been licensed for clinical trials by companies such as Ocata Therapeutics (formerly ACT). This effort received strong support from Yuan Capital and Yifang Ventures.

About Allele Biotechnology & Pharmaceuticals, Inc.

Allele Biotechnology and Pharmaceuticals, Inc. is a private, San Diego-based company that explores the mechanisms of biological processes to develop technologies and products for biomedical researchers. Allele utilizes proprietary non-integrating cellular reprogramming methods to generate human and non-human primate iPS cells, GMP-grade human iPS cells and their derivatives, and differentiated cell types. With additional expertise in genome modification and cell-based sensors/reporters, Allele provides advanced cell-based assays for drug discovery. Allele also has developed a wide variety of reagents including superior fluorescent proteins and camelid antibodies. The company has also been a leader in the RNAi field with its patents in Pol III promoter-driven siRNA, shRNA, and miRNA.

Contacts
Allele Biotechnology & Pharmaceuticals, Inc.
Matthew A. Singer, Ph. D.
Director of Business Development and Strategic Alliances
+1 858-587-6645, ext. 1
mattsinger@allelebiotech.com
www.allelebiotech.com

Tags: Allele iPSC, cell bank, cGMP, CIRM, GMP, iPSC, Mahendra Rao, NIH, personalized medicine, precision medicine, SAB, stem cell therapy