Crispr Genome Surgery In Stem Cells And Disease Tissues

CRISPR Genome Surgery in Stem Cells and Disease Tissues focuses uniquely on the clinical applications of CRISPR/Cas9 based technology. Topics include the latest advances in gene editing and its translational applications to various diseases, including retinal degenerative disease, recessively inherited diseases, and dominantly inherited diseases, to name a few. The book's target audience includes researchers, students, clinicians and the general public. This space that is not currently served by any existing resource, so this publication fills a gap in current literature. Provides a thorough review of CRISPR-Cas9, from discovery to therapy Covers the latest advances in gene editing and its translational applications to various diseases Written by global leaders in the fields of gene editing and stem cell therapy

This book presents descriptive overviews of gene editing strategies across multiple species while also offering in-depth insight on complex cases of application in the field of tissue engineering and regenerative medicine. Chapters feature contributions from leaders in stem cell therapy and biology, providing a comprehensive view of the application of gene therapy in numerous fields with an emphasis on ophthalmology, stem cells, and agriculture. The book also highlights recent major technological advances, including ZFN, TALEN, and CRISPR. Precision Medicine, CRISPR, and Genome Engineering is part of the highly successful Advances in Experimental Medicine and Biology series. It is an indispensable resource for researchers and students in genetics as well as clinicians.

Organ transplantation has been the most important therapeutic advance in the last third of the 20th century. Its development has revolutionized medicine, as demonstrated by the fact that a large number of researchers in this field have been awarded Nobel Prizes. In the beginning of this century, we are witnessing with great expectations the emergence of a new field of medicine related to the arrival of a new player on the scene: “stem cells” and their potential use in regenerative medicine. This volume aims to cover important aspects of the various facets of organ transplantation and regenerative medicine, with leading specialists in these fields setting out their vision. We try to rigorously explain current and novel scientific research in these fields—areas which arouse great interest from society in general, due to their potential use in modern medicine for the treatment of a great number of diseases.

Stem cells provide for life-long cell replacement in tissues and organs, and have inherent homing abilities that are critical in therapeutic applications. Stem cells are also the driving force of cancer where genetic/epigenetic alterations culminate in tumorigenesis either in tissue stem cells or in some of their derivatives. As a rare subset of the tumor, cancer stem cells are the only drive of tumor initiation/propagation. Autologous and cancer stem cells are thus the key targets of 1) long-term and transient-regenerative/epigenetic gene therapy and 2) of recurrence-free anticancer therapy, respectively. While cancer stem cell gene therapy still needs time to accomplish, autologous stem cells have been instrumental in the first unequivocal successes for gene therapy whereby ex vivo retrovirally corrected hematopoietic stem cells have been returned to the patients.This timely book presents 1) the aforementioned stem cell gene therapy achievements that rely on random-integration of therapeutic transgenes into host chromosomes and 2) emerging experimental approaches aimed at eliminating random-integration oncogenic hazards through site-specific integration or gene targeting. Breakthrough endonuclease-boosted gene targeting for gene correction (inherited diseases) or targeted integration of therapeutic transgenes (other disorders) culminating in an efficiency compatible with clinical trials is one of the highlights of the book. Highlights also include the pioneering transplantation of adult pluripotent stem cells as a substitute for tissue-specific stem cells, thereby pinpointing the invaluable potential for stem cell gene therapy applications of autologous cells able to contribute to all three germ layers. Stem cell gene therapy is thus discussed in terms of 1) magnifying stem cell therapeutic homing through transient regenerative gene therapy and 2) of tackling most pathologies (including mitochondrial DNA diseases and ageing disorders) through stem cell repopulation dynamics into appropriate niches (long-term engraftment) and tissues (cell turn-over). Regarding cancer stem cell gene therapy, focus is on both the increasing number of identified tissue-specific cancer stem cells as the ultimate therapeutic targets and on the development of armed stem cells as tumor-homing vectors for targeted anticancer therapy.

Precision genome surgery has the potential to revolutionize the field of personalized medicine through applications ranging from basic science, to creation of in vitro disease models, all the way to the correction of genetic disease in vivo. Although the field has rapidly advanced since the development of CRISPR-based technology, the ability to generate precise edits at multiple locations within the genome remains an outstanding challenge. As a result, edited cell populations as well as isolated clones must be rigorously screened for the presence of undesired mutations before any form of clinical application such as ex vivo cell therapy or in vivo somatic cell editing can be undertaken. Thus, there is a need to increase rates of precise editing and decrease rates of imprecise mutation to improve the clinical viability of gene editing. This thesis aims to develop new technologies to address challenges in precision genome editing and subsequently demonstrate their utility in a human pluripotent stem cell disease model. First, I describe a method to track hundreds of cell populations in real time using high-content analysis, allowing the facile selection of those that have undergone genome editing. Second, I demonstrate a new technology that is capable of tethering together CRISPR ribonucleoproteins and donor DNA to increase the frequency of precise gene surgery. Finally, I combine these technologies to correct mutations in an induced pluripotent stem cell model of Pompe disease, an autosomal recessive disorder. These methods and their applications demonstrate advances in the field of precision genome surgery and represent an important step toward the clinical use of genetic therapies.

Stem Cell Biology in Health and Disease presents an up-to-date overview about the dual role of stem cells in health and disease. The Editors have drawn together an international team of experts providing chapters which, in this fully-illustrated volume, discuss: - the controversial debate on the great expectations concerning stem cell based regeneration therapies raised by the pluripotency of various stem cells. - the advantages and concerns about embryonic stem cells (ES cells), induced pluripotent stem cells (iPS cells) and adult stem cells, such as bone marrow-derived stem cells (BMDCs). - the type of stem cells, which has become of interest in the past decade, namely so-called cancer stem cells (CSCs). CSCs are now in the focus of cancer research since the eradication of tumour initiating cells would raise the changes of definitely cure cancer. Professor Dittmar and Professor Zänker have edited a must-read book for researchers and professionals working in the field of regenerative medicine and/or cancer.

This book offers an updated overview of the most recent research advances in the field, a comparison of established techniques and methods, a discussion on current experimental and translational challenges, and a commentary on potential opportunities and future directions. Dedicated chapters address and review the preclinical and clinical state-of-the-art of gene therapies for the reconstructive and regenerative surgery of skin and wounds, pathological scars, cartilage, tendons, skeletal muscles, and bio-engineered flaps. A brief guide to developing gene therapy clinical trials in the context of reconstructive and regenerative surgery is also provided. Biomedical and technological innovations are transforming our capacity to use gene therapies to safely and effectively repair, reconstruct, and regenerate tissues that are deficient or have been damaged by trauma and diseases. The targeted and controlled modulation of gene expression in tissues represents a game-changing, next-generation therapeutic tool for the modern reconstructive surgeon, expanding the horizon of regenerative surgery and tissue engineering. Through gene therapies, surgeons can direct (stem) cell differentiation and cell function, modulate the release of growth/transcriptional factors, affect the biological properties of regenerative scaffolds, control tissue inflammation, or induce immune-suppression in composite tissue allotransplants and xenotransplants. Written by renowned reconstructive surgeons and leading experts in each of these fields - from top academic institutions around the globe, the book provides an initial practical guide for veteran and newcomer surgeons alike, as well as for researchers interested in exploring the latest gene-based therapeutic strategies for reconstructive and regenerative surgery.

Genome editing is a powerful new tool for making precise alterations to an organism's genetic material. Recent scientific advances have made genome editing more efficient, precise, and flexible than ever before. These advances have spurred an explosion of interest from around the globe in the possible ways in which genome editing can improve human health. The speed at which these technologies are being developed and applied has led many policymakers and stakeholders to express concern about whether appropriate systems are in place to govern these technologies and how and when the public should be engaged in these decisions. Human Genome Editing considers important questions about the human application of genome editing including: balancing potential benefits with unintended risks, governing the use of genome editing, incorporating societal values into clinical applications and policy decisions, and respecting the inevitable differences across nations and cultures that will shape how and whether to use these new technologies. This report proposes criteria for heritable germline editing, provides conclusions on the crucial need for public education and engagement, and presents 7 general principles for the governance of human genome editing.