Molecules for Gene Therapy -- Recent Progress in Non-viral Gene Delivery -- Physical Chemistry of DNA-Carrier Complexes -- Liposomes -- Polymeric Gene Carriers -- Development of a Supramolecular Nanocarrier for Gene Delivery Based on Cationic Block Copolymers -- Chitosan -- Dendrimers as DNA Carriers -- Use of Synthetic Peptides for Non-viral Gene Delivery -- An Oligonucleotide Carrier Based on ?-1,3-Glucans -- Biological and Chemical Hybrid Vectors -- Controlled Gene Delivery -- Pharmacokinetics of Gene Delivery in Cells -- Active DNA Release from Complexes -- Controlled Release of DNA Using Thermoresponsive Polymers -- Active Transport of Exogenous Genes into the Nucleus -- Controlled Intracellular Localization of Oligonucleotides by Chemical Conjugation -- Functional Nucleotide Sequences Capable of Promoting Non-viral Genetic Transfer -- Shielding of Cationic Charge of the DNA Complex to Avoid Nonspecific Interactions for In Vivo Gene Delivery -- In Vivo Gene Transfer by Ligand-Modified Gene Carriers -- Optimizing Polyplexes into Synthetic Viruses for Tumor-Targeted Gene Therapy -- Gene Transfer and Target Diseases -- Clinical Trials Using Non-viral Gene Delivery Systems -- Current Protocols of Gene Delivery -- Evaluation of Size and Zeta Potential of DNA/Carrier Complexes -- Observation of DNA/Carrier Complexes Under Fluorescence Microscopy -- Synthesis of Chemically Modified Chitosan and a Study of Its Gene Transfection Efficiency -- Newly Designed DNA Fragments for Gene Correction -- Evaluation of Gene Expression In Vivo After Intravenous and Intraportal Administration of Lipoplexes -- Evaluation by Southern Blot Hybridization of DNA Administered with a Gene Carrier to Organs -- Evaluation of the Immune Response After Administration of Plasmid DNA-Non-viral Vector Complexes -- Gateway RNAi -- Design of Genes Based on Current RNA Technology -- Design of Intracellularly Active Ribozymes and siRNAs -- RNAi-Based Inhibition Specific for Mutant Alleles in Autosomal Dominant Diseases: Sequence-Dependent and -Independent Discrimination of Mutant and Wild-Type Alleles by siRNA -- In Vivo RNA Interference: Another Tool in the Box? -- Suppression of Gene Expression via Chromatin Remodeling and the siRNA-Induced Silencing of Transcription -- Intracellular Delivery of Nucleic Acids: Differences Between Transfection and siFection Reflect Differences Between DNA and RNA, and Between Oligodeoxynucleotides and Oligonucleotides -- In Vivo Antitumor Activity of a New Cationic Liposome siRNA Complex -- Enhancing RNAi with Synthetic RNA Duplexes. Several years ago, when the discovery of catalytic RNA was recognized in a public manner,many people asked if new ?elds of therapy would soon be available. Although some tentative positive answers were given,nobody would say with certainty that RNA of various kinds was a truly promising means of altering gene expression. In fact,over the past decade,both our knowledge of RNAs with different functions and the utility of RNA in the inhibition or enhancement of gene expression have occurred with great drama. We proceeded in terms of possible therapeutic tools from RNase P and group I introns through "hammerhead" RNA enzymes, antisense technology, and more recently, to RNAi and its derivatives. A useful practical method of RNA delivery in animals will complete the picture. The diversity of RNA and the varied role of it inside cells and in therapy should be a tremendous challenge for young molecular biologists. This volume will make their task easier. Sidney Altman Sterling Professor of Molecular,Cellular & Devel- mental Biology,Nobel Laureate Department of Molecular,Cellular and Developm- tal Biology Yale University V NGTPR 4/23/05 1:00 PM Page VI VI Foreword Delivery of nucleic acids to cells in an animal remains a challenging problem. It is the major obstacle to success of therapeutic approaches using genes and oli- nucleotides,including siRNAs. Solutions found so far by chemists are satisfactory only for transfection of cells in culture.