University of Utah Research Foundation

Expression Genetics, Inc.

Sung Wan Kim

David A Bull

Miroslav Baudys

Feng Liu

You Han Bae

Darin Y Furgeson

Tae-il Kim

Won Jong Kim

Minhyung Lee

Ram I Mahato

Anurag Maheshwari

Atsushi Maruyama

Lei Yu

Teruo Okano

Sun Hwa Kim

Jindrich Henry Kopecek

Ji Hoon Jeong

Toshihiro Akaike

Pavla Kopeckova

Hye Yeong Nam

Jong Sang Park

Kihoon Nam

Lev I Valuev

Harold M Erickson

Helle Brondsted

James Yockman

Virginie Menard

Harvey Jacobs

Seongbong Jo

Young Hun Choi

Rafe C Connors

Soon H Yuk

Jin-Seok Kim

Jin Kim

James W Yockman

Jae-Woon Nah

Jonathan Brumbach

Cheol Hee Ahn

Lane V Christensen

The polymeric carrier for delivering nucleic acid material to a cell is provided herein. The polymeric carrier can include a dendrimer group having 2 to 8 termini, each of the termini having an arginine-grafted bioreducible polymer attached thereto. In one embodiment, only a portion of the termini can have an arginine-grafted bioreducible polymer attached thereto.

High molecular weight arginine-grafted bioreducible polymers

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.

Cleavable modifications to reducible poly(amido ethylenimine)s to enhance nucleotide delivery

A biologic ventricular assist device that also has the capability to capture, grow, and administer stem cells to regenerate and restore damaged myocardium in the heart. The device works in conjunction with a traditional ventricular assist device and possesses an additional external path or tube that is in-line with the path of the ventricular assist device. The external path allows for the administration of stem cells, genes, genetically modified cells or other therapeutic biologic or pharmacologic agents, as well as leading to a stem cell collecting accessory () that captures circulating stem cells. The stem cell collecting accessory is also associated with a chamber () for culturing the captured stem cells. The cultured stem cells can be delivered back to the heart by an electro-mechanical or ultrasound/echocardiographic delivery system that runs through the external path back into the ventricular assist device and allows for the delivery of the stem cells, or other therapeutic biologic or pharmacologic agents, directly into the internal chambers of the heart. Administering the stem cells, genes, genetically modified cells or other therapeutic biologic or pharmacologic agents, either alone or in combination, to the heart allows the myocardium to regenerate and repair itself even while the heart is attached to the ventricular assist device, ultimately allowing the heart to regenerate, recover and allow the VAD to be removed.

Ventricular assist device capable of implantation of stem cells

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 siRNA. ABP is biodegraded under reducing conditions, such as in the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity. ABP is an effective delivery vehicle for gene silencing with siRNA and may be used for treating cancer.

Arginine-conjugated bioreducible poly(disulfide amine) polymers for gene delivery system

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.

Arginine-conjugated bioreducible poly(disulfide amine) polymers for gene delivery systems

A carrier for delivering small interfering RNA (siRNA) into cells includes a cholesterol residue covalently bonded to oligoarginine. Mixing the siRNA with the carrier produces a complex-containing composition. Contacting a cell with the complex-containing composition results in delivery of the siRNA into the cell. Delivery of an siRNA targeted to vascular endothelial growth factor is a treatment for cancer. Methods of making the carrier and complex are also disclosed.

Polymeric carrier for delivery of small interfering RNA

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.

Hypoxia inducible VEGF plasmid for ischemic disease

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.

Linear polyethylenimine-sterol conjugates for gene delivery

A thermogelling, aliphatically modified polymer for use in drug delivery is described. Illustrative embodiments include poly(lactic-co-&#x3b5;-caprolactone)-poly(ethylene glycol)-poly(lactic-co-&#x3b5;-caprolactone) hexanoate and poly(lactic-co-&#x3b5;-caprolactone)-poly(ethylene glycol)-poly(lactic-co-&#x3b5;-caprolactone) laurate. Another illustrative embodiment includes a composition having a thermogelling amount of an aliphatically modified poly(lactic-co-&#x3b5;-caprolactone)-poly(ethylene glycol)-poly(lactic-co-&#x3b5;-caprolactone) and an effective amount of a drug. The thermogelling polymers are made by bonding an aliphatic group to poly(lactic-co-&#x3b5;-caprolactone)-poly(ethylene glycol)-poly(lactic-co-&#x3b5;-caprolactone). A method of use includes injecting a warm-blooded individual with a thermogelling amount of the aliphatically modified polymer and a drug.

Aliphatically modified biodegradable block copolymers as thermogelling polymers

Amphiphilic lipopeptide compositions for gene delivery are disclosed. An illustrative amphiphilic lipopeptide composition includes a human protamine 2 peptide conjugated to a hydrophobic moiety. Illustrative hydrophobic moieties include sterols, bile acids, and fatty acids. The amphiphilic lipopeptide composition is mixed with a nucleic acid such that the nucleic acid binds to the peptide portion of the lipopeptide. This mixture is placed in contact with mammalian cells to effect transfection of the cells with the nucleic acid. A method of making such amphiphilic lipopeptides is also described.

Soluble steroidal peptides for nucleic acid delivery

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.

Carrier system for specific artery wall gene delivery

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Salt Lake City, UT, United States of America

Sung Wan Kim