The challenge of vector development in gene therapy

Abstract

Gene therapy is the treatment of diseases based on the transfer of genetic information. Agents that carry or deliver DNA to target cells are called vectors (Latin vector: carrier, deliverer). Ideally, a vector should accommodate an unlimited amount of inserted DNA, lack the ability of autonomous replication of its own DNA, be easily manufactured, and be available in concentrated form. Secondly, it should have the ability to target specific cell types or to limit its gene expression to specific cell types, and to achieve sustained gene expression in the long term or in a controlled fashion. Finally, it should not be toxic or immunogenic. Such a vector does not exist and none of the DNA delivery systems so far available for in vivo gene transfer is perfect with respect to any of these points. Gene therapy and the means to promote it depend heavily on the development and improvement of new gene vector systems. Correspondence

Novel dextran–spermine conjugates as transfecting agents: comparing water-soluble and micellar polymers

“…3,4 The ideal gene delivery system must protect the nucleic acid from degradation, have the ability to deliver it to target cells, and should induce efficient gene expression in the presence of body fluids such as serum and interstitial fluids, concomitant with being nontoxic, nonimmunogenic, and stable during storage and treatment. [5][6][7] Gene delivery systems are classified into viral and nonviral systems, and the nonviral are subdivided into selfassembled and nonself-assembled systems. Although the actual in vivo transfection rates of the nonviral gene vectors are lower than those of viral vectors and the gene expression is transient, the nonviral systems offer several advantages, including increased biological safety, low immunogenicity, the ability to deliver large genes, and the possibility of large-scale production at reasonable cost.…”

Delivery of a transforming growth factor β-1 plasmid to mesenchymal stem cells via cationized Pleurotus eryngii polysaccharide nanoparticles

“…10 Nonviral gene vectors have emerged as a promising alternative to viral vectors because they offer such advantages as low immunogenicity, increased biological safety, the ability to deliver large genes, excellent flexibility in their building block structures, and the possibility of large-scale production at a reasonable cost. 11,12 As the leading nonviral gene vectors, cationic polymers can form complexes with the negatively charged nucleic acids so that large pieces of these nucleic acids can be condensed to nanometer-sized particles. This promotes the interaction of cationic polymers with the negatively charged cell membrane, which protects the incorporated nucleic acids in the complex from many types of degrading systems.…”

Pharmacokinetic Study of Viral Vectors for Gene Therapy: Progress and Challenges

“…In a word, gene therapy with viral vectors has been proven effective in a variety of model systems. However, studies have also shown that even if some common characteristics exist, an important variability is introduced by the administration route, the promoter and other key components of the construct (targeting modifications, etc) (Dani, S.U., 1999). The variability results in a variety of challenges, including circumvention of immune responses against viral vectors and difficulty in transferring the genes to a sufficient number of cells to change the phenotype, and in controlling the expression of the gene (Worgall, S. & Crystal, R.G., 2007).…”