Nonviral vectors such as liposomes are clearly nonpathogenic, but are also less efficient in the transfer of nucleic acid to the nucleus of cells. Adenoassociated virus vector as a platform for gene. The promise of gene therapy can be realized only if workable vectors can be found to deliver therapeutic genes. Viral vectors for use in gene therapy, cell therapy, and. Gene therapy for adascid, the first marketing approval of an ex vivo gene therapy in europe. Diseases free fulltext viral vectors in gene therapy.
The vector core is a full service core facility with over a decade of experience in the production of viral based vectors. In a range of human trials, viral vectors have emerged as safe and effective delivery vehicles for clinical gene therapy, particularly for monogenic recessive disorders, but there has also been early work on some idiopathic diseases. Recent advances in developing clinically desirable aav capsids, optimizing genome designs and harnessing revolutionary biotechnologies have contributed substantially to the growth of the gene therapy field. Methods and protocols, leading researchers from academia and biotechnology describe proven molecular methods for the construction, development, and use of virus vectors for gene transfer and gene therapy. One of the ratelimiting steps for successful gene therapy is the efficiency of gene transfer. A brief history of using viral vectors for gene therapy pioneering studies with ex vivo gene therapy for immunode. The viral genome comprises both genes and cisacting gene. Many types of viral vectors have been used in a wide array of basic and clinical studies, and genetic tools made possible to construct novel viruses intended for gene therapy, but also the. Viral vectors have become a fundamental tool among molecular biology researchers. These doublestranded dna vectors have the capacity to harbor. The most common viral vectors are outlined below, in. To this end, many vectors have been developed in which the endogenous viral envelope proteins have been replaced by either envelope proteins from other viruses. Gene therapy applications of viral vectors sage journals.
Adenoviruses are, in addition to retroviruses, the most applied viral vectors in gene therapy. Non viral vector as vaccine carrier weihsu claire chen and leaf huang. In gene therapy, viral vectors can be used for delivery of functional genes to replace defective genes to cure genetic disorders. Today,acquired diseases such as cancer 5,cardiovascular disease 6,neurodegenerative disorders 7 and infectious disease 8 are the subject of most gene therapy research fig. This attribute has led to extensive attempts to engineer recombinant viral vectors for the delivery of therapeutic genes into diseased tissues. As a vaccine platform, viral vectors can be used for expression and presentation of pathogenic antigens to induce an immune response by mimicking a natural infection. Examples of viral vectors applied for gene therapy. Fda has noted outside of the cmc draft guidance that viral vectors used for exvivo modification of cells should be treated as drug substances. While several genes with therapeutic potential have been identified, the best method of gene delivery is unknown. Article information, pdf download for viral vector systems for gene. Viral vectors based on adenovirus initially offered the ostensible promise of highly efficient, therapeutic in vivo gene delivery. Safe methods have been devised to do this, using several viral and nonviral vectors.
The vehicles used to introduce the transgene is known as vectors, the utility of the vector depends on the factor enlisted below. The huge potential for gene therapy to cure a wide range of diseases has led to high expectations and a great increase in research efforts in this area, particularly in the study of delivery via viral vectors, widely considered to be more efficient than dna transfection. The gene therapy program aims to discover transformative geneticbased therapeutics, which are translated to proofofconcept in clinical trials and commercialized through partnerships to assure access to patients in need. The main groups of viral vectors gene therapy was first conceived as a treatment for hereditary single gene defects 4. View enhanced pdf access article on wiley online library html view download pdf for offline viewing. Keywords gene therapy, risk assessment, viral vectors, occupational. Viruses as gene therapy vectors how gene therapy works. Why are viruses used in gene therapy viral vectors for gene therapy.
Recombinant viral vectors are genetic engineering tools commonly used for gene transfer purpose with high transfection efficiency and site specific gene insert slideshare uses cookies to improve functionality and performance, and to provide you with relevant advertising. These viral vectors have a number of specific advantages and disadvantages that make them suited to particular genetherapeutic applications. Viral vectors have been employed for the treatment of various diseases such as metabolic, cardiovascular, muscular, hematologic, ophthalmologic, and. Several viral vectorbased drugs have also been globally approved. Each of the vector systems has its strengths, as well as weaknesses, that require further modification to make the vector suited for general gene therapy applications. Retrovirus, adenovirus, and aav vectors are being evaluated currently in several phase 1 clinical trials for treatment of diseases such as cancer, cystic fibrosis, gaucher disease. Most gene therapy experiments have used viral vectors comprising elements of a virus that result in a replicationincompetent virus. Scalable purification of viral vectors for gene therapy. University of pennsylvania gene therapy program home. These successes have been enabled by research and development efforts focusing on vectors that combine low genotoxicity and immunogenicity with highly efficient. The desired characteristics of a viral vector for gene therapy are its easy purification into high titers to mediate targeted gene delivery and its prolonged gene expression with minimal side effects. Vectors for gene therapy viral and non viral virus, liposomes and naked dna are some of the vehicles used to introduce transgene into the host genome. Viruses have a natural ability to deliver genetic material into cells, and therefore some gene therapy products are derived from viruses.
Further, the first licensed gene therapy product in europe glybera involves an adenoassociated virus aav vector for the treatment of lipoprotein lipase deficiency, indicating that viral vectorbased gene therapy is becoming more relevant to translational research ylaherttuala, 2012. It is important to understand how these tools came about and the potential implications of their use. With the application of such viral vectors as clinical therapeutics growing, scalable commercial processes particularly for purification are. Significant improvements in vector engineering, delivery, and safety have placed viral vectorbased therapy at the forefront of modern medicine. Viral vectors for gene therapy methods and protocols. With the advent of more than 12 different gene therapy drugs for curing cancer, blindness, immune, and neuronal disorders, this emerging experimental medicine has yet again come in the limelight. Cruz, teresa rodrigues, marlene carmo, dagmar wirth, ana i. These properties make viruses attractive gene delivery vehicles, or vectors, for gene therapy. One of the basic concepts of gene therapy is to transform viruses into genetic shuttles, which will deliver the gene of interest into the target cells. Pdf manufacturing of viral vectors for gene therapy.
Recommendations for microbial vectors used for gene therapy. Viral vectors for gene therapy stanford university. Each viral vector system is characterized by an inherent set of properties that affect its suitability for specific gene therapy applications. Some viral vectors, for instance gammaretroviruses, insert their genomes at a seemingly random location on one of the host chromosomes, which can disturb the function of cellular genes and lead to cancer. Since these first vectors were developed, various vector systems have enjoyed rapid development and in the early days, transfer of. Gene therapy utilizes the delivery of dna into cells, which can be accomplished by several methods, summarized below. Pdf viral vectors for gene therapy steven ghivizzani. When so modified, such a virus can become a vehicle, or vector, to deliver a specific gene therapy. Frontiers gene therapy leaves a vicious cycle oncology. The use of viral vectors in gene therapy is an approach that has the potential for achieving direct, targeted in vivo delivery of the gene payload. Several types of viruses, including retrovirus, adenovirus, adenoassociated virus aav, and herpes simplex virus, have been modified in the laboratory for use in gene therapy applications. Today, researchers use several types of viruses as vectors. These are the major reasons why viral vectors derived from retroviruses, adenovirus, adenoassociated virus, herpesvirus and poxvirus are employed in more than 70% of clinical gene therapy trials.
Applications of viral vectors have found an encouraging new beginning in gene therapy in recent years. Viral vectors used for gene therapy based on the virus life cycle, infectious virions are very ef. Finally, the approval of viral vectorbased drugs is discussed. Many of these nonviral systems incorporate portions of viral vectors to increase the efficiency of gene delivery or expression. The two major classes of methods are those that use recombinant viruses sometimes called biological nanoparticles or viral vectors and those that use naked dna or dna complexes non viral methods. Comprehensive and authoritative, viral vectors for gene therapy. For the purposes of gene therapy, one might either want to limit or expand the range of cells susceptible to transduction by a gene therapy vector. As it turns out, this is completely possible as long as scientists modify the virus to prevent it from causing disease or inducing an immune reaction by the host. Gene therapy is the transfer of genetic material to a patients cells to achieve a therapeutic effect. Adenoassociated virus aav vectormediated gene delivery was recently approved for the treatment of inherited blindness and spinal muscular atrophy, and longterm therapeutic effects have been. Viral vector design and construction creative biolabs. Methods and protocols is a valuable resource for researchers, clinicians, and students looking to utilize viral vectors in gene therapy. The main groups of viral vectors applied for gene therapy are summarized below and in table1, followed by examples of both preclinical table2 and clinical. Gene therapy is the insertion of normal dna directly into a cell in order to correct genetic defects.
Viral vectors for gene therapy berkeley university of california. Gene therapy at the edge of impossible oxgene offers a range of viral technologies including aav, lentiviral and adenoviral vectors for license, as well as custom solutions to meet the manufacturing demands of new cell and gene therapies. Therapeutic dna is largely delivered using viral vector systems based on adenoviruses ad, adenoassociated viruses aav, and lentiviruses lv. Vectors in gene therapy an overview sciencedirect topics. In initial studies, immediate or immediate early genes were deleted.
Pdf gene therapy as part of modern molecular medicine holds great promise for the treatment of both acute and chronic diseases and has the potential. A number of different viral systems are being developed for use as vectors for ex viva and in vivo gene transfer, including retroviruses, adenoviruses, herpessimplex viruses and adenoassociated viruses. Steps toward a modern framework for the regulation of gene therapy. Engineering adenoassociated virus vectors for gene therapy.
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