Gene Transfer Technology in Therapy: Current Applications and Future Goals

Abstract

Gene therapy has attracted much interest since the first submissions of phase I clinical trials in the early 1990s, for the treatment of inherited genetic diseases. Preliminary results were very encouraging and prompted many investigators to submit protocols for phase I and phase II clinical trials for the treatment of inherited genetic diseases and cancer. The possible application of gene transfer technology to treat AIDS, cardiopathies, and neurologic diseases is under evaluation. Some viral vectors have already been used to deliver HIV-1 subunits to immunize volunteers who are participating in the AIDS vaccine programs in the USA. However, gene delivery systems still need to be optimized in order to achieve effective therapeutic interventions. The purpose of this review is to summarize the latest achievements in improving gene delivery systems, their current application in preclinical studies and in therapy, and the most pressing issues that must be addressed in the area of vector design.

Optimal modes and targets of gene therapy in transplantation

“…A number of different gene therapy delivery systems exist (2). For the purposes of our discussion, we will divide the major gene transfer systems into three groups: viral, liposomal, and naked DNA ( Table 2).…”

“…The biological characteristics of retroviruses are such that it enables them to exhibit broad cell tropism and effectively transduce many different cell types (5). Given the simplicity of the retroviral genome, replication-deficient viruses and viruses that can only infect once are easily produced, minimizing the risk of replication-competent virus formation (2). In addition, high levels of titers are achieved allowing for mass production of virus and enabling their use for clinical trials (2).…”

“…Given the simplicity of the retroviral genome, replication-deficient viruses and viruses that can only infect once are easily produced, minimizing the risk of replication-competent virus formation (2). In addition, high levels of titers are achieved allowing for mass production of virus and enabling their use for clinical trials (2). The ability of retroviral vectors to integrate into the host chromosome accounts for their stable gene expression and low level of immunogenicity.…”

An introduction to gene therapy and its potential prenatal use

“…In non-viral vector systems, there is no integration of introduced DNA, and therefore a transient expression of the therapeutic gene. Non-viral vectors include: direct transfer of therapeutic DNA into target cells (gene gun, direct DNA injection), liposomes (13), receptor mediated endocytosis (13), and mammalian artificial chromosomes (MAC). MAC do not require insertion into the genome and could include sufficient genomic sequences to ensure proper tissue-specific and temporal regulation.…”

“…Adenovirus vectors used in gene therapy are based on adenoviruses, which normally produce infections of the upper respiratory tract (11)(12)(13)16). The adenovirus vectors have several advantages; they can be produced in high titers in culture and they can infect many different human cell types, including both dividing and non-dividing cells.…”