Tools and Applications in Gene Therapy

The Gene Therapy field is living exciting times after more than 20 years of poor results. Many devastating human diseases are caused by mutations in a single gene that prevent a somatic cell from carrying out its essential functions, or by genetic changes acquired as a result of infectious disease or in the course of cell transformation. Targeted gene therapies have emerged as potential strategies for treatment of such diseases. These therapies depend upon rare-cutting endonucleases to cleave at specific sites in or near disease genes. Targeted gene correction provides a template for homology-directed repair, enabling the cell's own repair pathways to erase the mutation and replace it with the correct sequence. Targeted gene disruption ablates the disease gene, disabling its function. Gene targeting can also promote other kinds of genome engineering, including mutation, insertion, or gene deletion. Targeted gene therapies present significant advantages compared to approaches to gene therapy that depend upon delivery of stably expressing transgenes. Recent progress has been fueled by advances in nuclease discovery and design, and by new strategies that maximize efficiency of targeting and minimize off-target damage. Future progress will build on deeper mechanistic understanding of critical factors and pathways. The development of safer and more efficient gene transfer vectors and the advances on the cell therapy field have open new opportunities to tackle different diseases. Tools and Applications in Gene Therapy is intended to compile composed information about the different gene therapy tools, the clinical successes of gene therapy and the future applications. For the last two decades, retroviral vectors (RVs) have been major players in the fields of gene transfer and gene therapy. In the early 1980s, they were the first genetic vectors to permit an efficient and stable gene transfer into mammalian cells. In 1990, RVs were the first vectors used in a gene therapy clinical trial (for adenosine deaminase (ADA) deficiency). In 2000, after a decade of hopes and relative frustration, RVs were used in the first successful protocol that actually cured a genetic disease, demonstrating proof of concept for gene therapy. In all these years, vectors based on the Moloney murine leukaemia virus (MoMLV) have been pivotal in thousands of experiments, and continue to constitute the best tool available for stable gene transfer into a number of cell types and applications. Keys to their enormous success include the relative simplicity of their genomes, ease of use and their ability to integrate into the cell genome, permitting long-term transgene expression in the transduced cells or their progeny. The Gene Therapy field is living exciting times after more than 20 years of poor results. Many devastating human diseases are caused by mutations in a single gene that prevent a somatic cell from carrying out its essential functions, or by genetic changes acquired as a result of infectious disease or in the course of cell transformation. Targeted gene therapies have emerged as potential strategies for treatment of such diseases. These therapies depend upon rare-cutting endonucleases to cleave at specific sites in or near disease genes. Targeted gene correction provides a template for homology-directed repair, enabling the cell's own repair pathways to erase the mutation and replace it with the correct sequence. Targeted gene disruption ablates the disease gene, disabling its function. Gene targeting can also promote other kinds of genome engineering, including mutation, insertion, or gene deletion. Targeted gene therapies present significant advantages compared to approaches to gene therapy that depend upon delivery of stably expressing transgenes. Recent progress has been fueled by advances in nuclease discovery and design, and by new strategies that maximize efficiency of targeting and minimize off-target damage. Future progress will build on deeper mechanistic understanding of critical factors and pathways. The development of safer and more efficient gene transfer vectors and the advances on the cell therapy field have open new opportunities to tackle different diseases. Tools and Applications in Gene Therapy is intended to compile composed information about the different gene therapy tools, the clinical successes of gene therapy and the future applications. For the last two decades, retroviral vectors (RVs) have been major players in the fields of gene transfer and gene therapy. In the early 1980s, they were the first genetic vectors to permit an efficient and stable gene transfer into mammalian cells. In 1990, RVs were the first vectors used in a gene therapy clinical trial (for adenosine deaminase (ADA) deficiency). In 2000, after a decade of hopes and relative frustration, RVs were used in the first successful protocol that actually cured a genetic disease, demonstrating proof of concept for gene therapy. In all these years, vectors based on the Moloney murine leukaemia virus (MoMLV) have been pivotal in thousands of experiments, and continue to constitute the best tool available for stable gene transfer into a number of cell types and applications. Keys to their enormous success include the relative simplicity of their genomes, ease of use and their ability to integrate into the cell genome, permitting long-term transgene expression in the transduced cells or their progeny. The Gene Therapy field is living exciting times after more than 20 years of poor results. Many devastating human diseases are caused by mutations in a single gene that prevent a somatic cell from carrying out its essential functions, or by genetic changes acquired as a result of infectious disease or in the course of cell transformation. Targeted gene therapies have emerged as potential strategies for treatment of such diseases. These therapies depend upon rare-cutting endonucleases to cleave at specific sites in or near disease genes. Targeted gene correction provides a template for homology-directed repair, enabling the cell's own repair pathways to erase the mutation and replace it with the correct sequence. Targeted gene disruption ablates the disease gene, disabling its function. Gene targeting can also promote other kinds of genome engineering, including mutation, insertion, or gene deletion. Targeted gene therapies present significant advantages compared to approaches to gene therapy that depend upon delivery of stably expressing transgenes. Recent progress has been fueled by advances in nuclease discovery and design, and by new strategies that maximize efficiency of targeting and minimize off-target damage. Future progress will build on deeper mechanistic understanding of critical factors and pathways. The development of safer and more efficient gene transfer vectors and the advances on the cell therapy field have open new opportunities to tackle different diseases. Tools and Applications in Gene Therapy is intended to compile composed information about the different gene therapy tools, the clinical successes of gene therapy and the future applications. For the last two decades, retroviral vectors (RVs) have been major players in the fields of gene transfer and gene therapy. In the early 1980s, they were the first genetic vectors to permit an efficient and stable gene transfer into mammalian cells. In 1990, RVs were the first vectors used in a gene therapy clinical trial (for adenosine deaminase (ADA) deficiency). In 2000, after a decade of hopes and relative frustration, RVs were used in the first successful protocol that actually cured a genetic disease, demonstrating proof of concept for gene therapy. In all these years, vectors based on the Moloney murine leukaemia virus (MoMLV) have been pivotal in thousands of experiments, and continue to constitute the best tool available for stable gene transfer into a number of cell types and applications. Keys to their enormous success include the relative simplicity of their genomes, ease of use and their ability to integrate into the cell genome, permitting long-term transgene expression in the transduced cells or their progeny.