Gene therapy strategies for AIDS-related malignancies

Curiel, Tyler J.; Piché, Alain; Kasono, Keizo; Curiel, DT

doi:10.1038/sj.gt.3300538

Cited by 7 publications

(4 citation statements)

References 6 publications

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“…This line of treatment offers new hope for survival against many diseases which have genetic origins like cancer [2], diabetes [3], cystic fibrosis [4], AIDS [5] and cardiovascular diseases [6] etc. This strategy has broadened the scope of playing with the genetic material to avoid, remove or replace the fundamental cause of the diseases by delivering the desired genes or oligonucleotides or by blocking the ‘disease-causing’ sequence from transcription and translation.…”

Section: Introductionmentioning

confidence: 99%

Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

et al. 2013

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BackgroundSix new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)n- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media.Methodology/Principal FindingsTo understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features.Conclusions/Significance-OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies.

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Section: Introductionmentioning

confidence: 99%

Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

et al. 2013

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“…Gene Therapy , which involves the transfer of a desired gene to a target cell, is a new hope for various disorders like cystic fibrosis , , diabetes, cancer , , AIDS, and so forth − . The first major challenge of the use of gene therapy for curing disorders is to deliver the desired gene efficiently with the least toxicity and low immunogenicity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Gene Transfection Efficacies of PEI−Cholesterol-Based Lipopolymers

2008

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Nine lipopolymers based on low molecular weight polyethyleneimines (PEI) and cholesterol via an ether linkage between the polymer amine and the cholesterol backbone have been synthesized. Different percentage of cholesterol moieties have been grafted on three types of PEI of molecular weights 800, 1200, and 2000. These lipopolymers were studied for gene transfection activities in HeLa cells. All the lipopolymers were first optimized for enhanced transfection efficacies as coliposomes with DOPE. All lipopolymers are better transfecting agents and highly serum compatible than commercially available PEI-25KDa. Transfection efficacies and serum compatibility of lipopolymers were found to be dependent upon the MW of PEI used for lipopolymer synthesis and percentage of cholesterol grafting on lipopolymers. Cell viability assay showed that PEI-25KDa is highly toxic as compared to all the lipopolymers. Lipopolyplexes were characterized by transmission electron microscopy, which showed the presence of spherical aggregates.

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“…Hence, there has been a significant increase in AIDS-related malignancies in the past 10 years (16). The different gene therapy strategies for these malignancies were recently reviewed (15). Of note, sFvs have been employed in this context also.…”

Section: Genetic Interventions For Hiv Infectionsmentioning

confidence: 99%

“…Intracellular immunization-based strategies are also being considered for AIDS-related malignancies (15). With the improvement of antiviral therapy and prophylaxis against opportunistic infections, HIV patients are now living longer.…”

Section: Genetic Interventions For Hiv Infectionsmentioning

confidence: 99%

Gene Therapy for HIV Infections: Intracellular Immunization

Piché

1999

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Despite significant advances in the treatment of human immunodeficiency virus (HIV) infection in the past 10 years, it remains an incurable disease. The inability of traditional drug-based therapies to inhibit HIV replication effectively for extended periods of time has stimulated intense research to develop novel approaches for this disease. Current understanding of HIV molecular biology and pathogenesis has opened the way for the development of gene therapy strategies for HIV infections. In this context, a number of intracellular immunization-based strategies have been evaluated, and some of them have reached the stage of phase I/II human clinical trials. These strategies include the use of single-chain antibodies, capsid-targeted viral inactivation, transdominant negative mutants, ribozymes, antisense oligonucleotides and RNA decoys. While a number of issues remain to be studied before intracellular immunization can be applied to the treatment of HIV infections, the significant progress already made in this field is likely to lead to clinical applications.

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Gene therapy strategies for AIDS-related malignancies

Cited by 7 publications

References 6 publications

Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

Synthesis and Gene Transfection Efficacies of PEI−Cholesterol-Based Lipopolymers

Gene Therapy for HIV Infections: Intracellular Immunization

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