Designer gene delivery vectors: molecular engineering and evolution of adeno-associated viral vectors for enhanced gene transfer.


:Gene delivery vectors based on adeno-associated virus (AAV) are highly promising due to several desirable features of this parent virus, including a lack of pathogenicity, efficient infection of dividing and non-dividing cells, and sustained maintenance of the viral genome. However, several problems should be addressed to enhance the utility of AAV vectors, particularly those based on AAV2, the best characterized AAV serotype. First, altering viral tropism would be advantageous for broadening its utility in various tissue or cell types. In response to this need, vector pseudotyping, mosaic capsids, and targeting ligand insertion into the capsid have shown promise for altering AAV specificity. In addition, library selection and directed evolution have recently emerged as promising approaches to modulate AAV tropism despite limited knowledge of viral structure-function relationships. Second, pre-existing immunity to AAV must be addressed for successful clinical application of AAV vectors. "Shielding" polymers, site-directed mutagenesis, and alternative AAV serotypes have shown success in avoiding immune neutralization. Furthermore, directed evolution of the AAV capsid is a high throughput approach that has yielded vectors with substantial resistance to neutralizing antibodies. Molecular engineering and directed evolution of AAV vectors therefore offer promise for generating 'designer' gene delivery vectors with enhanced properties.


Pharm Res


Pharmaceutical research


Kwon I,Schaffer DV




Has Abstract


2008-03-01 00:00:00












  • Effect of von Willebrand factor on the pharmacokinetics of recombinant human platelet glycoprotein Ibalpha-immunoglobulin G1 chimeric proteins.

    abstract:PURPOSE:Recombinant human platelet glycoprotein Ibalpha-immunoglobulin G1 chimeric proteins (GPIbalpha-Ig) have varying levels of anti-thrombotic activities based on their ability to compete for platelet mediated adhesion to von Willebrand Factor (vWF). Valine substituted GPIbalpha-Ig chimeras, at certain position, inc...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Wang Q,Shorten D,Xu X,Shaw GD,Schaub RG,Shea C,Brooks J,Sako D,Wiswall E,Xu J,Szklut P,Patel VS

    更新日期:2006-08-01 00:00:00

  • Population Pharmacokinetics of Sulindac and Genetic Polymorphisms of FMO3 and AOX1 in Women with Preterm Labor.

    abstract:PURPOSE:This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS:Plasma samples were collected at 1.5, 4, and 10 h after first oral ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Sung JW,Yun HY,Park S,Kim YJ,Yee J,Lee KE,Song B,Chung JE,Gwak HS

    更新日期:2020-01-28 00:00:00

  • A theoretical basis for a biopharmaceutic drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability.

    abstract::A biopharmaceutics drug classification scheme for correlating in vitro drug product dissolution and in vivo bioavailability is proposed based on recognizing that drug dissolution and gastrointestinal permeability are the fundamental parameters controlling rate and extent of drug absorption. This analysis uses a transp...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Amidon GL,Lennernäs H,Shah VP,Crison JR

    更新日期:1995-03-01 00:00:00

  • Enhanced Anti-Tumor Efficacy of Lipid-Modified Platinum Derivatives in Combination with Survivin Silencing siRNA in Resistant Non-Small Cell Lung Cancer.

    abstract:PURPOSE:Cisplatin, is recognized as a first line therapeutic for the treatment of non-small cell lung cancer (NSCLC). Cisplatin resistance is identified as the most detrimental complication during treatment and has been associated with upregulation of several genes, such as the anti-apoptotic gene survivin. In this stu...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Mattheolabakis G,Ling D,Ahmad G,Amiji M

    更新日期:2016-12-01 00:00:00

  • Enhancement of nasal salmon calcitonin absorption by lauroylcarnitine chloride in rats.

    abstract:PURPOSE:We investigated optimum formulation characteristics in the nasal absorption of salmon calcitonin (sCT) by incorporation of acylcarnitines. METHODS:Nasal sCT formulations were administered to anesthetized rats. Plasma calcium level was measured and pharmacological bioavailability (P.bioav) was calculated. RESU...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kagatani S,Shinoda T,Fukui M,Ohmura T,Hasumi S,Sonobe T

    更新日期:1996-05-01 00:00:00

  • Dual-Targeted Delivery of Nanoparticles Encapsulating Paclitaxel and Everolimus: a Novel Strategy to Overcome Breast Cancer Receptor Heterogeneity.

    abstract:PURPOSE:The intratumoral heterogeneity observed in breast cancer (BC), in particular with regard to cell surface receptor expression, can hinder the success of many targeted cancer therapies. The development of novel therapeutic agents that target more than one receptor can overcome this inherent property of tumors and...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Houdaihed L,Evans JC,Allen C

    更新日期:2020-01-21 00:00:00

  • Identification of human UDP-glucuronosyltransferase responsible for the glucuronidation of niflumic acid in human liver.

    abstract:PURPOSE:To assess the uridine diphosphate (UDP)-glucuronosyltransferase (UGT) isozymes involved in the glucuronidation of niflumic acid in human liver. METHODS:The glucuronidation activity of niflumic acid was determined in liver microsomes and recombinant UGT isozymes by incubation of niflumic acid with UDP-glucuroni...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Mano Y,Usui T,Kamimura H

    更新日期:2006-07-01 00:00:00

  • Protein spray-freeze drying. Effect of atomization conditions on particle size and stability.

    abstract:PURPOSE:To investigate the effect of atomization conditions on particle size and stability of spray-freeze dried protein. METHODS:Atomization variables were explored for excipient-free (no zinc added) and zinc-complexed bovine serum albumin (BSA). Particle size was measured by laser diffraction light scattering follow...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Costantino HR,Firouzabadian L,Hogeland K,Wu C,Beganski C,Carrasquillo KG,Córdova M,Griebenow K,Zale SE,Tracy MA

    更新日期:2000-11-01 00:00:00

  • PLGA microparticles in respirable sizes enhance an in vitro T cell response to recombinant Mycobacterium tuberculosis antigen TB10.4-Ag85B.

    abstract:PURPOSE:To study the use of poly (lactide-co-glycolide) (PLGA) microparticles in respirable sizes as carriers for recombinant tuberculosis (TB) antigen, TB10.4-Ag85B, with the ultimate goal of pulmonary delivery as vaccine for the prevention of TB. MATERIALS AND METHODS:Recombinant TB antigens were purified from E. co...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Shi S,Hickey AJ

    更新日期:2010-02-01 00:00:00

  • Estimation of the degree of crystallinity of cefazolin sodium by X-ray and infrared methods.

    abstract::The pentahydrate (alpha form) of cefazolin sodium (CEZ) exhibited sharp X-ray diffraction peaks, while the dehydrated alpha form showed weak but distinct diffraction peaks. As expected the amorphous form exhibited a diffuse and halo diffraction pattern. The X-ray procedure to estimate the degree of crystallinity of CE...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Kamat MS,Osawa T,DeAngelis RJ,Koyama Y,DeLuca PP

    更新日期:1988-07-01 00:00:00

  • Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats.

    abstract:PURPOSE:The pharmacokinetics of corticosteroids in pregnancy were analyzed to assess maternal/fetal disposition and factors controlling fetal exposure. Area/Moment equations and compartmental models for estimating pharmacokinetic parameters from single dose data during pregnancy were developed. METHODS:Betamethasone i...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Samtani MN,Schwab M,Nathanielsz PW,Jusko WJ

    更新日期:2004-12-01 00:00:00

  • A new mathematical model quantifying drug release from bioerodible microparticles using Monte Carlo simulations.

    abstract:PURPOSE:The major objectives of this study were to 1) develop a new mathematical model describing all phases of drug release from bioerodible microparticles; 2) evaluate the validity of the theory with experimental data; and 3) use the model to elucidate the release mechanisms in poly(lactide-co-glycolide acid)-based m...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Siepmann J,Faisant N,Benoit JP

    更新日期:2002-12-01 00:00:00

  • Mechanistic studies on effervescent-induced permeability enhancement.

    abstract:PURPOSE:To determine the mechanism(s) by which effervescence induces penetration enhancement of a broad range of compounds ranging in size, structure, and other physiocochemical properties across rat and rabbit small intestinal epithelium. METHODS:Effervescent induced penetration enhancement was investigated in vitro ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Eichman JD,Robinson JR

    更新日期:1998-06-01 00:00:00

  • Potential of immobilized artificial membranes for predicting drug penetration across the blood-brain barrier.

    abstract:PURPOSE:The present study evaluates immobilized artificial membrane (IAM) chromatography for predicting drug permeability across the blood-brain barrier (BBB) and outlines the potential and limitations of IAMs as a predictive tool by comparison with conventional methods based on octanol/water partitioning and octadecyl...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Reichel A,Begley DJ

    更新日期:1998-08-01 00:00:00

  • Photokinetic Drug Delivery: Near infrared (NIR) Induced Permeation Enhancement of Bevacizumab, Ranibizumab and Aflibercept through Human Sclera.

    abstract:PURPOSE:Permeation studies, with near infrared (NIR) light and anti-aggregation antibody formulation, were used to investigate the in vitro permeation of bevacizumab, ranibizumab and aflibercept through human sclera. METHODS:A vertical, spherical Franz cell diffusion apparatus was used for this scleral tissue permeati...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Giannos SA,Kraft ER,Zhao ZY,Merkley KH,Cai J

    更新日期:2018-03-29 00:00:00

  • Immobilization of active urokinase on albumin microspheres: use of a chemical dehydrant and process monitoring.

    abstract::A method of immobilizing urokinase on albumin microspheres has been developed. Laser scattering, which was used to follow particle size from the initial emulsification stage to the final aqueous resuspension of the microsphere stage, showed that particle coalescence and crosslinking were critical parameters in manufac...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Bhargava K,Ando HY

    更新日期:1992-06-01 00:00:00

  • Subcellular distribution of basic drugs accumulated in the isolated perfused lung.

    abstract::To clarify the mechanism by which basic drugs accumulate in the lung, the binding selectivity of drugs to different subcellular structures of the perfused rat lung was examined. Imipramine, quinine, and metoclopramide were used as examples of basic drugs. The accumulation of basic drugs was highest in the mitochondria...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Yoshida H,Okumura K,Hori R

    更新日期:1987-02-01 00:00:00

  • Efficacy of Optimized Treatment Protocol Using LAU-7b Formulation against Ovalbumin (OVA) and House Dust Mite (HDM) -Induced Allergic Asthma in Atopic Hyperresponsive A/J Mice.

    abstract:PURPOSE:To assess the efficacy of the novel clinical formulation of fenretinide (LAU-7b) for the treatment of allergic asthma. To study the association between LAU-7b treatment in allergic asthma and the modulation of very long chain ceramides (VLCC). METHODS:We used two allergens (OVA and HDM) to induce asthma in mou...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Youssef M,De Sanctis JB,Kanagaratham C,Tao S,Ahmed E,Radzioch D

    更新日期:2020-01-08 00:00:00

  • Pharmacokinetics and pharmacodynamics of PEGylated IFN-beta 1a following subcutaneous administration in monkeys.

    abstract:PURPOSE:To characterize the pharmacokinetic/pharmacodynamic (PK/PD) properties of a new polyethylene glycol (PEG) conjugate formulation of interferon (IFN)-beta la following subcutaneous (SC) administration in monkeys. METHODS:Single SC injections of 0.3, 1, and 3 million international units (MIU)/kg of PEG-IFN-beta 1...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Mager DE,Neuteboom B,Jusko WJ

    更新日期:2005-01-01 00:00:00

  • Human monoclonal antibody fragments targeting matrilin-3 in growth plate cartilage.

    abstract:PURPOSE:Many genetic disorders, including chondrodysplasias, and acquired disorders impair growth plate function, resulting in short and sometimes malformed bones. There are multiple endocrine and paracrine factors that promote chondrogenesis at the growth plate, which could potentially be used to treat these disorders...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Cheung CS,Zhu Z,Lui JC,Dimitrov D,Baron J

    更新日期:2015-07-01 00:00:00

  • Elucidation of Molecular Mechanisms Behind the Self-Assembly Behavior of Chitosan Amphiphilic Derivatives Through Experiment and Molecular Modeling.

    abstract:PURPOSE:Chitosan-based polymeric micelles (CBPMs) are considered as promising carriers for delivery of anticancer drugs, imaging agents and genes. To optimize the physicochemical, pharmaceutical and biological properties of CBPMs, the molecular mechanisms behind the self-assembly behavior of chitosan (CHI) amphiphilic ...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Mahmoudzadeh M,Fassihi A,Dorkoosh F,Heshmatnejad R,Mahnam K,Sabzyan H,Sadeghi A

    更新日期:2015-12-01 00:00:00

  • Crystal growth kinetics of theophylline monohydrate.

    abstract::The crystal growth kinetics of theophylline monohydrate from aqueous buffered supersaturated solutions were investigated at 10, 20, 30, and 40 degrees C. Crystallization experiments were carried out isothermally at pH 6. During growth the crystal count and size distributions were monitored in situ. The growth rate was...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Rodríguez-Hornedo N,Wu HJ

    更新日期:1991-05-01 00:00:00

  • Nose-to-brain transport pathways of wheat germ agglutinin conjugated PEG-PLA nanoparticles.

    abstract:PURPOSE:To investigate the possible pathways for transport of wheat germ agglutinin conjugated PEG-PLA nanoparticles (WGA-NP) into the brain after nasal administration. METHODS:The nose-to-brain pathways were investigated using WGA-NP containing 6-coumarin (as a fluorescent marker) and (125)I-labeled WGA-NP. Ex vivo i...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Liu Q,Shen Y,Chen J,Gao X,Feng C,Wang L,Zhang Q,Jiang X

    更新日期:2012-02-01 00:00:00

  • IL-1Ra and its delivery strategies: inserting the association in perspective.

    abstract::Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring anti-inflammatory antagonist of interleukin-1 family of pro-inflammatory cytokines. The broad spectrum anti-inflammatory effects of IL-1Ra have been investigated against various auto-immune diseases such as diabetes mellitus, rheumatoid arthritis. Des...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审


    authors: Akash MS,Rehman K,Chen S

    更新日期:2013-11-01 00:00:00

  • Access to the CNS: Biomarker Strategies for Dopaminergic Treatments.

    abstract::Despite substantial research carried out over the last decades, it remains difficult to understand the wide range of pharmacological effects of dopaminergic agents. The dopaminergic system is involved in several neurological disorders, such as Parkinson's disease and schizophrenia. This complex system features multipl...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章,评审


    authors: van den Brink WJ,Palic S,Köhler I,de Lange ECM

    更新日期:2018-02-15 00:00:00

  • Polydopamine-based surface modification for the development of peritumorally activatable nanoparticles.

    abstract:PURPOSE:To create poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), where a drug-encapsulating NP core is covered with polyethylene glycol (PEG) in a normal condition but exposes a cell-interactive TAT-modified surface in an environment rich in matrix metalloproteinases (MMPs). METHODS:PLGA NPs were modified w...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Gullotti E,Park J,Yeo Y

    更新日期:2013-08-01 00:00:00

  • Effect of Permeation Enhancers on the Buccal Permeability of Nicotine: Ex vivo Transport Studies Complemented by MALDI MS Imaging.

    abstract:PURPOSE:The purpose of this study was to assess the effect of several chemical permeation enhancers on the buccal permeability of nicotine and to image the spatial distribution of nicotine in buccal mucosa with and without buccal permeation enhancers. METHODS:The impact of sodium taurodeoxycholate (STDC), sodium dodec...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Marxen E,Jin L,Jacobsen J,Janfelt C,Hyrup B,Nicolazzo JA

    更新日期:2018-02-21 00:00:00

  • Drug delivery studies in Caco-2 monolayers. IV. Absorption enhancer effects of cyclodextrins.

    abstract:PURPOSE:The purpose of the present study was to use the human colorectal carcinoma cell line. Caco-2, as a human intestinal epithelial model for studying the effects of cyclodextrins as absorption enhancers. METHODS:Cyclodextrins of varying sizes and physicochemical characters were investigated. The effects of the cyc...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: Hovgaard L,Brøndsted H

    更新日期:1995-09-01 00:00:00

  • Dissolution techniques for in vitro testing of dry powders for inhalation.

    abstract:PURPOSE:To evaluate different dissolution testing methods and subsequently develop a simple to perform but reproducible and discriminating dissolution technique for inhalative powders. METHODS:From a dry powder a fraction of aerosolized particles with an aerodynamic particle size below 5 μm was collected on regenerate...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: May S,Jensen B,Wolkenhauer M,Schneider M,Lehr CM

    更新日期:2012-08-01 00:00:00

  • In situ determination of delavirdine mesylate particle size in solid oral dosage forms.

    abstract:PURPOSE:The in-situ particle size of delavirdine mesylate in dry mix and tablets was determined. METHODS:Optical microscopy and fluorescence microscopy combined with image analysis were used for qualitative and quantitative measurements. RESULTS:Using optical microscopy, it was demonstrated qualitatively that fragmen...

    journal_title:Pharmaceutical research

    pub_type: 杂志文章


    authors: White JG

    更新日期:1999-04-01 00:00:00