Abstract:
An artery wall binding peptide (AWBP) based on the artery wall cell-binding domain of apolipoprotein B-100 was conjugated to a cationic backbone configured for forming a complex with a nucleic acid to produce a composition that enhances gene transfer to artery wall cells. An illustrative cationic backbone is poly(ethylene glycol)-grafted-poly(L-lysine) (PEG-g-PLL). Methods of making and using the composition for gene transfer are also described.
Abstract:
A biodegradable, novel cationic coopolymer comprising a a poly(alkylenimine)(PAI), a hydrophilic polymer, and a biodegradable linker, wherein the biodegradable linker covalently links the PAI and the hydrophilic polymer. The biodegradable cationic copolymers in the present invention can be used in drug delivery and are especially useful for delivery of a nucleic acid or any anionic bioactive agent to various organs and tissues after local or systemic administration.
Abstract:
Poly[&agr;-(4-aminobutyl)-L-glycolic acid] (PAGA) is disclosed as a biodegradable composition suitable for delivering a gene into a cell. Methods of making and using PAGA are also disclosed.
Abstract:
Improved poly(amido ethylenimine) copolymers for gene delivery are disclosed. One illustrative embodiment includes polyethylene glycol (PEG) covalently bonded to a branched poly(triethyenetetramine/cystamine bisacrylamide) copolymer (poly(TETA/CBA)). The polyethylene glycol can be linear or branched. Another illustrative embodiment includes an RGD peptide covalently bonded to the poly(TETA/CBA)-PEG conjugate. Still another illustrative embodiment includes a method of using these compositions for transfecting a cell with a nucleic acid.
Abstract:
Plasmids useful for treating ischemic disease, such as ischemic heart disease, are described. The plasmids express vascular endothelial growth factor (VEGF) under the control of a promoter (RTP801) that is up-regulated under hypoxic conditions. Pharmaceutical compositions for treating ischemic disease include mixtures of the hypoxia-regulated VEGF plasmids and pharmaceutically acceptable carriers. Methods for treating ischemic disease include administering such pharmaceutical compositions to a person in need of such treatment.
Abstract:
Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.
Abstract:
Polyplex formulations were prepared using p(TETA/CBA), its PEGylated analog, p(TETA/CBA)-g-PEG2k, and mixtures of the two species at 10/90 and 50/50 wt %, respectively. Increasing PEG wt % inhibited polyplex formation. This work demonstrates the feasibility of preparing homogenous polyplexes by altering the PEG wt % using a mixture of p(TETA/CBA) and p(TETA/CBA)-g-PEG2k products. Further, a single-step method of making p(TETA/CBA)-g-PEG2k is disclosed.
Abstract:
An arginine-grafted bioreducible poly(disulfide amine) (“ABP”) as a reagent for efficient and nontoxic gene delivery is described. ABP forms positively charged nano-particles of less than 200 nm with plasmid DNA. ABP is biodegraded under reducing conditions, such as the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity.
Abstract:
Plasmids useful for treating ischemic disease, such as ischemic heart disease, are described. The plasmids express vascular endothelial growth factor (VEGF) under the control of a promoter (RTP801) that is up-regulated under hypoxic conditions. Pharmaceutical compositions for treating ischemic disease include mixtures of the hypoxia-regulated VEGF plasmids and pharmaceutically acceptable carriers. Methods for treating ischemic disease include administering such pharmaceutical compositions to a person in need of such treatment.
Abstract:
Linear polyethylenimine was modified with sterols, such as cholesterol, in three different geometries: linear shaped (L), T-shaped (T), and a combined linear- and T-shaped (LT), to result in linear polyethylenimine-sterol conjugates. These conjugates were mixed with nucleic acids to form complexes for delivery of the nucleic acids into cells. Mammalian cells transfected with these complexes showed protein expression levels higher than linear polyethylenimine alone, and twice that of branched polyethylenimine, but without any significant loss in cell viability. Methods of making these compositions and methods of using them for gene delivery are also described.