Targeted, non-viral gene delivery for cancer gene therapy.
The ability to mediate targeted and specific delivery of therapeutics to cancer cells remains one of the most important hurdles in effectively treating cancer. This aspect also remains as one of the greatest limitations of gene therapy as well. Targeted vectors based on the use of DNA-binding agents attached to cell specific ligands or "molecular conjugates" were created with the goal of over-coming this hurdle. Since being conceived, many different ligands have been utilized as molecular conjugates, targeting the resulting Protein/DNA polyplex to cells efficiently in vitro while mediating limited delivery in vivo. This limited delivery is due to many reasons such as the need to identify non-viral agents that can aide in escaping endosome entrapment as well as decreasing the complexity that has evolved in the creation of these "synthetic viruses". This review will discuss the current status and the future of molecular conjugates as targeting vectors as well as the positive and negative attributes of this vector in relation to other viral and non-viral vectors that are currently used in many gene therapy strategies.
Cristiano
R J
RJ
Section of Thoracic Molecular Oncology, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 109, Houston, Texas 77030, USA. rcristia@notes.mdacc.tmc.edu
D004268:DNA-Binding Proteins / Q000502:physiology; D016503:Drug Delivery Systems; D011992:Endosomes / Q000502:physiology; D005544:Forecasting; D018390:Gene Targeting; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000628:therapy*; D009696:Nucleic Acids / Q000627:therapeutic use; D011956:Receptors, Cell Surface / Q000502:physiology
D004268:DNA-Binding Proteins; D008024:Ligands; D009696:Nucleic Acids; D011956:Receptors, Cell Surface