Biomedical subjects

Minhyung Lee

Publications and source records attributed to Minhyung Lee.

At least 19 recordsLinked to original sources

PubMed2006

A hypoxia-inducible gene expression system using erythropoietin 3' untranslated region for the gene therapy of rat spinal cord injury.

Many neurologic disorders are accompanied by ischemic injury during the pathologic process. To develop a controllable and injury-specific gene therapy system for the neurologic disorders, we constructed a hypoxia inducible plasmid with the erythropoietin (Epo) 3' untranslated region (UTR), which can enhance the stability of target mRNAs in response to hypoxia. The Epo 3' UTR was inserted at the 3' flanking region of luciferase gene in pSV-Luc, resulting in the construction of pSV-Luc-EpoUTR. In pEpo-SV-Luc-EpoUTR, the Epo enhancer was inserted into the upstream of the SV40 promoter to increase the hypoxia inducibility. The plasmids were evaluated in N2a mouse neuroblastoma cells under hypoxic conditions and in a rat spinal cord injury (SCI) model. The results showed that the Epo 3' UTR alone showed a three-fold increase in luciferase activity in hypoxic N2a cells as well as in the rat SCI model when compared to the sham control. In contrast, the Epo 3' UTR showed no effect on the luciferase activity in the presence of the Epo enhancer, probably because the Epo enhancer was more sensitive to hypoxia and showed a dominant effect. However, the Epo enhancer itself showed high level of luciferase activity even in normoxia (about five to eight-folds increase), while the Epo 3' UTR did not show enhanced background activity. Immunohistochemical staining showed expression of luciferase from pSV-Luc-EpoUTR both in neurons and astrocytes around the injured spinal cord of rat. These results suggest that the Epo 3' UTR could provide a specific and safe system for the hypoxia-inducible gene therapy of the neurologic disorders including SCI.

3' Untranslated Regions↗

PubMed2006

Dexamethasone conjugated poly(amidoamine) dendrimer as a gene carrier for efficient nuclear translocation.

Nuclear membrane is one of the main barriers in polymer-mediated intracellular gene delivery. It was previously reported that glucocorticoid receptor dilated the nuclear pore and translocated into nucleus when it bound to its ligand, glucocorticoid. This suggests that the transport of DNA into nucleus may be facilitated by glucocorticoid. In this study, a glucocorticoid, dexamethasone, was conjugated to polyamidoamine (PAMAM) dendrimer and the effect of the conjugation was investigated. The PAMAM-Dexamethasone (PAM-Dexa) was synthesized by the one-step reaction using Traut's reagent. PAM-Dexa/plasmid DNA complex was completely retarded at a 1/1 weight ratio (polymer/DNA) in a gel retardation assay. PAM-Dexa protected DNA from DNase I for more than 60 min. PAM-Dexa/plasmid DNA complex showed the highest transfection efficiency to 293 cells at a 0.8/1 weight ratio. At this ratio, PAM-Dexa had higher transfection efficiency than PAMAM. Especially in the presence of serum during the transfection, the transfection efficiency of PAM-Dexa was higher than that of PAMAM or PEI by one order of magnitude. In addition, more PAM-Dexa/DNA complexes were observed in the nucleus region than PAMAM/DNA from the confocal microscopy studies. These results indicated that the technique with dexamethasone might be useful for the gene delivery using polymeric gene carriers and the development of efficient polymer vectors.

Active Transport, Cell Nucleus↗

PubMed2006

An efficient GLP-1 expression system using two-step transcription amplification.

Glucagon-like peptide 1 (GLP-1) is an insulinotropic protein. It was reported that the continuous infusion of GLP-1 normalized the blood glucose level in type 2 diabetes animal model. However, the short half-life of GLP-1 has limited its application in clinical settings and prompted us to develop a GLP-1 gene therapy system. Our previous results showed that the delivery of pbeta-GLP-1 using polyethylenimine (PEI) reduced the blood glucose level effectively. However, the glucose level was not completely normalized. In the present study, the more efficient GLP-1 expression system was developed using two-step transcription amplification (TSTA). To evaluate the TSTA system, pbeta-Gal4-p65 and pUAS-Luc were constructed. The pUAS-Luc/pbeta-Gal4-p65 system showed the highest transfection efficiency at a 2:1 pUAS-Luc/pbeta-Gal4-p65 weight ratio. In addition, the transgene expression by the TSTA system was at least 4 times higher than pbeta-Luc. To apply the TSTA system to the GLP-1 expression plasmid, pUAS-GLP-1 was constructed. The pUAS-GLP-1/pbeta-Gal4-p65 system showed higher mRNA level than pbeta-GLP-1. In addition, the level of GLP-1 by the pUAS-GLP-1/pbeta-Gal4-p65 system was more than 4 times higher than pbeta-GLP-1. Therefore, the TSTA GLP-1 expression system may be useful to develop gene therapy system for type 2 diabetes.

Cell Line↗

PubMed2006

Hypoxia-inducible gene expression system using the erythropoietin enhancer and 3'-untranslated region for the VEGF gene therapy.

Gene therapy with the vascular endothelial growth factor (VEGF) gene is a potential treatment for many disorders or injuries with ischemia. However, unregulated expression of VEGF may induce pathological angiogenesis, promoting tumor growth, diabetic proliferative retinopathy and rupture of atherosclerotic plaque. Therefore, the effective regulation of the gene expression is one of the requirements for the VEGF gene therapy. In this research, we evaluated the hypoxia-inducible gene expression system with the erythropoietin (Epo) enhancer and the Epo 3'-untranslated region (UTR). The luciferase plasmids were constructed with the Epo enhancer (pEpo-SV-Luc), the Epo 3'-UTR (pSV-Luc-EpoUTR) or both (pEpo-SV-Luc-EpoUTR). The polyethylenimine/plasmid complexes were transfected to 293 or A7R5 cells and the cells were incubated under normoxia or hypoxia. The results showed that the Epo enhancer or Epo 3'-UTR increased the target gene expression under hypoxia. pEpo-SV-Luc-EpoUTR showed the highest luciferase expression. The VEGF expression plasmid with the Epo enhancer and 3'-UTR was also constructed. The VEGF expression by pEpo-SV-VEGF-EpoUTR showed the highest specificity of the gene expression in the hypoxic cells. The results suggest that the VEGF plasmid with the Epo enhancer and the Epo 3'-UTR may be useful for gene therapy for ischemic diseases.

3' Untranslated Regions↗

PubMed2006

Enhanced transfection of primary cortical cultures using arginine-grafted PAMAM dendrimer, PAMAM-Arg.

PAMAM-Arg is a cationic arginine-grafted polyamidoamine (PAMAM) dendrimer. In the previous study, we reported that PAMAM-Arg facilitates transfection in a range of mammalian cell types. In the present study, we investigated the transfection efficiency of PAMAM-Arg in primary cortical cultures, which are known to be extremely vulnerable to exogenous gene transfection. PAMAM-Arg/DNA complexes showed particularly high transfection efficiencies and low cytotoxicity in primary cortical cells, as compared to other gene carriers such as, native PAMAM, polyethylenimine (BPEI), and Lipofectamine. Efficient transfection was not limited to neurons but extended to all three glial cells, astrocytes, microglia, and oligodendrocytes, present in these primary cortical cultures. The potential use of PAMAM-Arg was demonstrated by efficient gene knock-down by transfecting HMGB1 shRNA-expressing plasmid. The numbers of green fluorescent protein (GFP)-positive and HMGB1-negative cells indicated that PAMAM-Arg/shRNA-expressing plasmid complex suppressed target gene expression in over 40% of cells, which is the highest level achieved to date in primary cortical culture by any gene carrier. Here, we present evidence of the successful delivery and expression of both a reporter gene and of a shRNA-expressing plasmid in primary cortical cells, which demonstrates the potential of PAMAM-Arg for mediating gene delivery to primary neuronal cells.

Animals↗

PubMed2006

Non-viral adiponectin gene therapy into obese type 2 diabetic mice ameliorates insulin resistance.

Synthetic polymer vectors are attractive for gene delivery due to their potential safety and versatility. However, due to the low efficiency, most of the successful applications of polymeric vectors are focused on the therapeutic genes whose products have biological effects at low concentrations. Adiponectin is one of the abundant circulating proteins and possesses diverse effects including anti-hyperglycemic and anti-atherogenic properties. In this study, we performed the adiponectin gene delivery using a mini-circle DNA complexed with a polymeric carrier, polyethylenimine, into diet induced obese C57BL/6J mice. The mini-circle DNA showed much higher adiponectin expression than the conventional plasmid in vitro and in vivo. This strategy achieved a sufficient blood level of adiponectin and the parameters related with insulin resistance were normalized. The mini-circle DNA will be useful for the increased efficiency of polymeric vectors and adiponectin gene therapy which is applicable to the treatment of type 2 diabetes.

AMP-Activated Protein Kinases↗

PubMed2006

Anti-angiogenic inhibition of tumor growth by systemic delivery of PEI-g-PEG-RGD/pCMV-sFlt-1 complexes in tumor-bearing mice.

Vascular endothelial growth factor (VEGF) is an endogenous mediator of tumor angiogenesis. Blocking associations of the VEGF with its corresponding receptors (Flt-1, KDR/flk-1) have become critical for anti-tumor angiogenesis therapy. Previously, we synthesized PEI-g-PEG-RGD conjugate and evaluated as an angiogenic endothelial polymeric gene carrier. In this study, PEI-g-PEG-RGD/pCMV-sFlt-1 complexes are evaluated in terms of tumor growth inhibition in vivo. Complexes were repeatedly injected systemically via tail vein into subcutaneous tumor-bearing mice. As a result, tumor growth was inhibited in the PEI-g-PEG-RGD/pCMV-sFlt-1 injected group. However, this effect was not identified in PEI-g-PEG/pCMV-sFlt-1 or PEI-g-PEG-RGD/pCMV-GFP control groups. Moreover, the survival rate increased in the PEI-g-PEG-RGD/pCMV-sFlt-1 group compared with the controls group. These results suggest that delivery of pCMV-sFlt-1 using PEG-g-PEG-RGD may be effective for anti-angiogenic gene therapy.

Angiogenesis Inhibitors↗

PubMed2006

Interleukin-10 plasmid construction and delivery for the prevention of type 1 diabetes.

Studies of animals with spontaneous autoimmune diabetes have revealed that autoreactive T cells that mediate islet beta cell destruction can be manipulated by the administration of Th(2) cytokines. In this article, the effect of interleukin-10 (IL-10) gene delivery was evaluated in vitro and in vivo with a novel IL-10 plasmid, pSI-IL-10-NFkappaB. In pSI-IL-10-NFkappaB, the expression of the IL-10 gene was driven by the SV40 promotor/enhancer. The nuclear factor kappaB (NFkappaB) binding sites were also introduced to facilitate nuclear transport of the plasmid in the cell. In vitro transfection assay with pSI-IL-10-NFkappaB showed a similar expression level of IL-10 to the plasmid without NFkappaB binding sites (pSI-IL-10). pSI-IL-10-NFkappaB and pSI-IL-10 were intravenously injected into 5-week-old nonobese diabetic (NOD) mice using polyethylenimine (PEI) as a gene carrier. Both groups had persistent gene expression, longer than 5 weeks, and secreted the similarly high IL-10 serum levels. Interestingly, the degree of insulitis in the pSI-IL-10-NFkappaB group was improved over the pSI-IL-10 group, PEI-only group, and noninjected controls. The serum glucose levels showed that single injection of pSI-IL-10-NFkappaB prevented the development of diabetes in 100% of the pSI-IL-10-NFkappaB-injected animals (5/5), while that of pSI-IL-10 prevented diabetes in 40% of the treated animals (2/5). These results suggest that pSI-IL-10-NFkappaB with PEI can effectively reduce the incidence of insulitis and type 1 diabetes in NOD mice.

Animals↗

PubMed2005

Combined angiopoietin-1 and vascular endothelial growth factor gene transfer restores cavernous angiogenesis and erectile function in a rat model of hypercholesterolemia.

Hypercholesterolemia-related endothelial cell dysfunction and decreased endothelium-derived nitric oxide formation may account for impaired angiogenesis and subsequent erectile dysfunction. Angiopoietin-1 (Ang1) is a critical angiogenic factor for vascular maturation and enhances vascular endothelial growth factor (VEGF)-induced angiogenesis in a complementary manner. We hypothesized that combined adenovirus-delivered human Ang1 (ad-Ang1) and VEGF165 (ad-VEGF165) gene transfer might promote angiogenesis cooperatively in a rat model of hypercholesterolemic erectile dysfunction and result in a recovery of erectile function. Ad-Ang1 and ad-VEGF165 were injected either alone or in combination into the corpus cavernosum of the penis. Combined gene transfer of both ad-Ang1 and ad-VEGF165 significantly increased cavernous angiogenesis, eNOS phosphorylation, and cGMP expression compared with that in the groups treated with either therapy alone. Erectile function, as evaluated by electrical stimulation of the cavernous nerve 2 and 8 weeks after treatment, was completely restored in the combined treatment group, whereas intracavernous injection of either ad-Ang1 or ad-VEGF165 alone elicited partial improvement. The results indicate that combined application of angiogenic factors may enhance cavernous angiogenesis cooperatively by reinforcing the endothelium both structurally and functionally, which results in an additive effect on erectile function in hypercholesterolemic rats.

Adenoviridae↗

PubMed2005

Ischemic injury-specific gene expression in the rat spinal cord injury model using hypoxia-inducible system.

STUDY DESIGN: A spinal cord injury and in vitro neural hypoxia models were used to evaluate the hypoxia responsive gene expression. OBJECTIVES: To limit the risk of unwanted overexpression of therapeutic genes, we developed a hypoxia-inducible gene therapy system using the erythropoietin (Epo) enhancer and the RTP801 promoter. SUMMARY OF BACKGROUND DATA: Gene therapy is an emerging therapeutic technique to treat spinal cord injury. However, uncontrolled overexpression of therapeutic genes in nondisease tissues during gene therapy raises a doubt about its safety. Post-traumatic ischemia is an important factor worsening the spinal cord damage, and hypoxia could regulate the gene expressions using a hypoxia-inducible promoter. METHODS: The plasmids, pEpo-SV-Luc and pRTP801-Luc, were constructed. Mouse neuroblastoma cells (N2A) were used to evaluate the hypoxia-inducible gene expression in vitro.- Gene transfection and expression were allowed for 24 hours under normoxia (pO2, 152 mm Hg) or hypoxia (pO2, 7.6 mm Hg). Spinal cord injury was made using clip compression. Plasmids were injected directly into the injured spinal cord immediately following injury. The gene expression was assessed by luciferase assay. RESULTS: pEpo-SV-Luc and pRTP801-Luc showed more than three times higher gene expression in N2A cells under hypoxia than normoxia. The expression level of luciferase in the injured spinal cord was higher than in the normal spinal cord. Immunostaining demonstrated that neurons, astrocytes, and capillary endothelial cells expressed luciferase in the cytoplasm. CONCLUSIONS: The pEpo-SV-Luc and pRTP801-Luc systems are effective in that they induce gene expression specifically in neurons under the hypoxic condition and spinal cord injury.

Animals↗

PubMed2005

Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier.

To develop chitosan based efficient gene carriers, highly purified chitosan oligosaccharides (COSs) were chemically modified with deoxycholic acid (DOCA). Owing to the amphiphilic characters, the DOCA-conjugated COSs (COSDs) formed self-aggregated nanoparticles in aqueous milieu. The physicochemical characterization revealed that the particle size of the nanoparticles was in the range of 200 approximately 240 nm and the critical aggregation concentration (cacs) was 0.012 approximately 0.046 g/L, depending on the degree of substitution (DS). As efficient gene carriers, the COSD nanoparticles showed superior gene condensation and protection of condensed gene from endonuclease attack than unmodified COSs. Furthermore, COSDs showed great potential for gene carrier with the high level of gene transfection efficiencies, even in the presence of serum. Considered with the negligible cytotoxic effects, DOCA-modified chitosan oligosaccharides can be considered as potential candidates for efficient non-viral gene carriers.

Chemical Phenomena↗

PubMed2005

Anti-GAD antibody targeted non-viral gene delivery to islet beta cells.

An islet cell targeting polymeric gene carrier was synthesized by conjugating anti-GAD Fab' fragment to PEI via PEG linker (PEI-PEG-Fab'). The Fab' fragment was prepared from a murine monoclonal antibody against glutamic acid decarboxylase (GAD), which has been identified as one of the major auto-antigens expressed in islet cells, and used as a targeting moiety for islet cell targeting. The electrophoretic migration of plasmid DNA (pCMVLuc)/PEI-PEG-Fab' complexes in agarose gel was completely retarded above the N/P ratio of 2. The complexes demonstrated a size of 100-275 nm with an almost neutral surface charge. Confocal microscopy revealed that the PEI-PEG-Fab' complexes showed much higher cellular binding and uptake efficiency compared to PEI-PEG complexes. The PEI-PEG-Fab' showed about 10-fold higher transfection efficiency (relative luciferase activity) than PEI-PEG in GAD-expressing mouse insulinoma cells (MIN6), however the transfection efficiency of PEI-PEG-Fab' reduced to that of PEI-PEG in GAD negative cells (293) and in the presence of competitive free Fab'. Considering the neutral surface charge of its complexes with DNA, and selectivity toward the islet cells expressing a specific antigen, the PEI-PEG-Fab' conjugate could be thought as a potential candidate of the systemic gene therapy for the treatment of type I diabetes.

Animals↗

PubMed2005

Soluble Flt-1 gene delivery using PEI-g-PEG-RGD conjugate for anti-angiogenesis.

Vascular endothelial growth factor (VEGF), a potent angiogenic molecule specific for vascular endothelial cells, is overexpressed in most tumors and closely associated with tumor growth and metastasis. It has been shown that a soluble fragment of VEGF receptor Flt-1 (sFlt-1) has anti-angiogenic properties by way of its antagonist activity against VEGF. In the present study, we demonstrated that the stable expression of sFlt-1 by endothelial cell targeted non-viral gene delivery inhibited the angiogenesis of endothelial cells. A targeted polymeric gene delivery system, PEI-g-PEG-RGD, was developed by incorporating the alphanubeta3/alphanubeta5 integrin-binding RGD peptide, ACDCRGDCFC (single-letter amino acid code), into the cationic polymer, polyethylenimine (PEI) via a hydrophilic polyethylene glycol (PEG) spacer. The functional analysis of therapeutic gene encoding sFlt-1/carrier complex was performed with an endothelial cell proliferation assay. The complex of sFlt-1 gene with PEI-g-PEG-RGD conjugate efficiently inhibited the proliferation of cultured endothelial cells, representing that expressed sFlt-1 predominantly bound to exogenous VEGF and blocked the binding of VEGF to the full-length Flt-1 receptor. These findings suggest that the combination of targeted gene carrier and sFlt-1 possesses the potential to be an efficient tool for the anti-angiogenic gene therapy to treat cancer.

Angiogenesis Inhibitors↗

PubMed2005

Glucagon-like peptide-1 plasmid construction and delivery for the treatment of type 2 diabetes.

Glucagon-like peptide-1 (GLP-1) is a 30-amino-acid hormone produced by intestinal L cells. It has been proposed that GLP-1 can be used as a new treatment for type 2 diabetes mellitus because it acts to augment insulin secretion and its effectiveness is maintained in type 2 diabetic patients. Despite its many remarkable advantages as a therapeutic agent for diabetes, GLP-1 is not immediately clinically applicable because of its extremely short half-life. One way to overcome this drawback is GLP1 gene delivery, which enables GLP-1 production in the body. In this study, the effect of GLP1 gene delivery was evaluated both in vitro and in vivo using a new plasmid constructed with a GLP1 (7-37) cDNA. The expression of the GLP1 gene was driven by a SV40 promoter/enhancer. To increase the expression level of GLP-1, nuclear factor kappaB binding sites were introduced. The in vitro results showed expression of GLP-1 and in vitro activity of GLP-1, which is a glucose-dependent insulinotropic action. A single systemic administration of polyethyleneimine/pSIGLP1NFkappaB complex into DIO mice resulted in increasing insulin secretion and decreasing blood glucose levels for a duration longer than 2 weeks.

Animals↗

PubMed2005

Polymeric gene carrier for insulin secreting cells: poly(L-lysine)-g-sulfonylurea for receptor mediated transfection.

Ex vivo transfer of therapeutic genes to cells is one of the potential strategies to prolong the life span of cell transplants. However, relatively safe non-viral carriers have not been extensively investigated due to their lower transfection efficiency. In this study, poly(L-lysine)-g-sulfonylurea varying SU content (PLL-SU) was synthesized to promote gene delivery efficacy to an insulin secreting cell line, RINm5F, which is known to express sulfonylurea receptor (SUR). The polymer formed complexes with a model reporter gene of pCMV-Luc (DNA) and the size of resulting particles was around 100 nm. The transfection efficiency of a polymer synthesized with 5 mol% of SU in the reaction feed (PLL-SU5%) to RINm5F cell was at least 5 times higher than that of PLL. The cytotoxicity of PLL-SU5%/DNA complex was equivalent to that of PLL/DNA complex. PLL-SU5% showed less transfection efficiency than PLL to NIH3T3 and HepG2 cells which are SUR negative. In RINm5F cells, the addition of free SU decreased the transfection efficiency of PLL-SU5%/DNA complex, suggesting that the complex shares the same receptors for SU. The PLL-SU5%/DNA complex seems to be internalized via SUR-mediated endocytosis pathway as suggested by vacuolar ATPases inhibition by Bafilomycin A1. It is noted that RINm5F cells treated with PLL-SU5%/DNA complex secreted more insulin than control, untreated cells, suggesting the insulinotropic effect of SU in PLL-SU5%. In conclusion, PLL-SU may be useful for transfer of therapeutic genes into insulin secreting cells.

Animals↗

PubMed2005

Preparation of large monodispersed spherical silica particles using seed particle growth.

To obtain large-sized, monodispersed spherical particles of silica by sol precipitation, a seed particle growth method was attempted. The formation of secondary particles during seed particle growth causing a multimodal distribution of particle size was suppressed via fine adjustment of the reaction conditions, such as TEOS, ammonia, and water concentrations, as well as operational conditions such as feeding time and agitation speed. Among the reaction conditions, an increase of TEOS concentration promoted secondary particle formation, resulting in bimodal particle distribution. However, secondary particle formation was depressed with increasing ammonia and water concentrations. In addition, long feeding time (low feed flow rate) and rigorous agitation significantly reduced secondary particle formation because they contributed to the slow generation of supersaturation and rapid seed particle growth, respectively.

Journal Article↗

PubMed2005

Local, non-viral IL-12 gene therapy using a water soluble lipopolymer as carrier system combined with systemic paclitaxel for cancer treatment.

Development of improved gene transfer methods is needed for gene therapy to achieve its clinical potential. The use of biocompatible polymeric gene carriers has shown effectiveness in overcoming the current problems associated with viral vectors in safety, immunogenicity and mutagenesis. Previous work has demonstrated that repeated, local, non-viral interleukin-12 (IL-12) gene delivery successfully slows down tumor progression, while improving immunogenicity. Combining IL-12 gene delivery with systemic paclitaxel (PCT) chemotherapy as a treatment for various subcutaneous mouse mammary carcinomas, we used PCT with either a biodegradable polymeric solubilizer, HySolv or Cremophor EL for systemic treatment and injected water soluble lipopolymer (WSLP)/plasmid-encoding IL-12 gene (p2CMVmIL-12) complexes local once every week. The amount of lung metastases being essential for survival as well as subcutaneous tumor volume were compared against untreated controls. We showed inhibition of tumor growth and decreased lung metastases in the combined WSLP/p2CMVmIL-12/HySolv group compared to the controls and the PCT only treated groups. Compared to Cremophor, HySolv performed better alone or in combination with IL-12. Using polymeric vectors as gene carrier systems in combination with improved systemic therapies provide evidence for the efficacy and feasibility of polymer-based drug delivery systems. Especially local cytokine gene delivery showed augmentation of systemic chemotherapy while reducing the hosts risk for further systemic toxicity.

Animals↗

PubMed2005

Polyethylene glycol-conjugated copolymers for plasmid DNA delivery.

Polymeric gene delivery systems have been developed as an alternative for viral gene delivery systems to overcome the problems in the use of viral gene carriers. Polymeric carriers have many advantages as gene carriers such as low cytotoxicity, low immunogenicity, moderate transfection efficiency, no size-limit, low cost, and reproducibility. In the efforts to develop safe and efficient polymeric gene carriers, polyethylene glycol (PEG) has widely been used because of its excellent characteristics. PEG-conjugated copolymers have advantages for gene delivery: (1) The PEG-conjugated copolymers show low cytotoxicity to cells in vitro and in vivo, (2) PEG increases water-solubility of the polymer/DNA complex, (3) PEG reduces the interaction of the polymer/DNA complex with serum proteins and increases circulation time of the complex, 4) PEG can be used as a spacer between a targeting ligand and a cationic polymer. A targeting ligand at the end of a PEG chain is not disturbed by the interaction of a cationic polymer with plasmid DNA, and the PEG spacer increases the accessibility of the ligand to its receptor. In this review, PEG copolymers as gene carriers are introduced, and their characteristics are discussed.

Animals↗