Strategies to achieve targeted gene delivery via the receptor-mediated endocytosis pathway. 1994

S I Michael, and D T Curiel
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham 35294, USA.

Gene transfer to eukaryotic cells may be accomplished by capitalizing on endogenous cellular pathways of macromolecular transport. In this regard, molecular conjugate vectors have been developed which deliver DNA via the receptor-mediated endocytosis pathway. An attractive feature of this vector system is the potential to achieve targeted gene delivery based upon flexible incorporation of a targeting ligand. In this review we describe steps that have been taken to optimize this vector system. Specific strategies include the incorporation of mechanisms to achieve conjugate escape from the endosome and the derivation of methods to eliminate sources of nonspecificity. These developments have demonstrated the potential to construct a vector system in which multiple independent components may function in a concerted manner to accomplish targeted high efficiency gene delivery. In their present state of development, molecular conjugate vectors may have many potential applications for in vitro use.

UI MeSH Term Description Entries
D011107 Polylysine A peptide which is a homopolymer of lysine. Epsilon-Polylysine,Poly-(Alpha-L-Lysine),Epsilon Polylysine
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D011991 Receptors, Virus Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response. Viral Entry Receptor,Viral Entry Receptors,Virus Attachment Factor,Virus Attachment Factors,Virus Attachment Receptor,Virus Attachment Receptors,Virus Entry Receptor,Virus Entry Receptors,Virus Receptor,Virus Receptors,Attachment Factor, Virus,Attachment Factors, Virus,Attachment Receptor, Virus,Attachment Receptors, Virus,Entry Receptor, Viral,Entry Receptor, Virus,Entry Receptors, Viral,Entry Receptors, Virus,Receptor, Viral Entry,Receptor, Virus,Receptor, Virus Attachment,Receptor, Virus Entry,Receptors, Viral Entry,Receptors, Virus Attachment,Receptors, Virus Entry
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004705 Endocytosis Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis. Endocytoses
D005822 Genetic Vectors DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition. Cloning Vectors,Shuttle Vectors,Vectors, Genetic,Cloning Vector,Genetic Vector,Shuttle Vector,Vector, Cloning,Vector, Genetic,Vector, Shuttle,Vectors, Cloning,Vectors, Shuttle
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000256 Adenoviridae A family of non-enveloped viruses infecting mammals (MASTADENOVIRUS) and birds (AVIADENOVIRUS) or both (ATADENOVIRUS). Infections may be asymptomatic or result in a variety of diseases. Adenoviruses,Ichtadenovirus,Adenovirus,Ichtadenoviruses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018014 Gene Transfer Techniques The introduction of functional (usually cloned) GENES into cells. A variety of techniques and naturally occurring processes are used for the gene transfer such as cell hybridization, LIPOSOMES or microcell-mediated gene transfer, ELECTROPORATION, chromosome-mediated gene transfer, TRANSFECTION, and GENETIC TRANSDUCTION. Gene transfer may result in genetically transformed cells and individual organisms. Gene Delivery Systems,Gene Transfer Technique,Transgenesis,Delivery System, Gene,Delivery Systems, Gene,Gene Delivery System,Technique, Gene Transfer,Techniques, Gene Transfer,Transfer Technique, Gene,Transfer Techniques, Gene

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