Stem cells, ribozymes and HIV

Burnett, J.; Rossi, John J.

doi:10.1038/gt.2009.86

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…While all of these trials have demonstrated the safety and feasibility of gene-delivered ribozyme therapy, none has proven a clear survival advantage for the protected cells vs. the empty vector (control) transduced cells. This might be due to the poor engraftment of transduced cells, limited efficacy of the therapeutic ribozyme, chromatin silencing of the integrated ribozyme, suboptimal ribozyme kinetics, or other possible factors [85]. …”

Section: Catalytic Rnas: Ribozymesmentioning

confidence: 99%

“…In particular, Bevasiranib and AGN-745, two intravitreally injected naked siRNAs for the treatment of AMD and DME, were terminated due to the lack of patient improvement and TLR-mediated inflammation [30, 31]. Other RNA-based drugs, including the Bcr-Abl and TKM-ApoB siRNAs and several anti-HIV ribozymes, have been discontinued due to insufficient in vivo drug efficacy [47, 85, 86]. Therefore, the future progress of RNA therapeutics relies heavily on improvements in the design of RNA drugs and delivery technologies that can improve drug efficacy and minimize off-target effects.…”

Section: Design and Deliverymentioning

confidence: 99%

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RNA-Based Therapeutics: Current Progress and Future Prospects

Burnett

Rossi

2012

Chemistry & Biology

810

593

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Summary Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprecedented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes.

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Section: Catalytic Rnas: Ribozymesmentioning

confidence: 99%

Section: Design and Deliverymentioning

confidence: 99%

RNA-Based Therapeutics: Current Progress and Future Prospects

Burnett

Rossi

2012

Chemistry & Biology

810

593

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“…Patients underwent chemotherapy‐based conditioning prior to transplantation, which enhances the engraftment of the transduced HPCs 7. Since patients in this trial required treatment of NHL in addition to HIV, autologous stem cell therapy offered a potential therapy for both diseases.…”

Section: Ex Vivo Deliverymentioning

confidence: 99%

Current progress of siRNA/shRNA therapeutics in clinical trials

Burnett

Rossi

Tiemann

2011

Biotechnology Journal

398

312

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Through a mechanism known as RNA interference (RNAi), small interfering RNA (siRNA) molecules can target complementary mRNA strands for degradation, thus specifically inhibiting gene expression. The ability of siRNAs to inhibit gene expression offers a mechanism that can be exploited for novel therapeutics. Indeed, over the past decade, at least 21 siRNA therapeutics have been developed for more than a dozen diseases, including various cancers, viruses, and genetic disorders. Like other biological drugs, RNAi-based therapeutics often require a delivery vehicle to transport them to the targeted cells. Thus, the clinical advancement of numerous siRNA drugs has relied on the development of siRNA carriers including biodegradable nanoparticles, lipids, bacteria, and attenuated viruses. Most therapies permit systemic delivery of the siRNA drug, while others use ex vivo delivery by autologous cell therapy. For some of the drugs, advancements in bioengineering and nanotechnology have led to improved control of delivery and release of the siRNA. Likewise, progress in molecular biology has allowed for improved design of the siRNA molecules. Here, we provide an overview of siRNA therapeutics in clinical trials, including their clinical progress, the challenges they have encountered, and the future they hold in the treatment of human diseases.

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“…Insertions of genes with their own promoters may generate risks from long-term expression or insertional activation of nearby genes (Burnett and Rossi, 2009; Li et al, 2005; Tiemann and Rossi, 2009). The expressed proteins may also be immunogenic in the recipient, limiting the expansion or lifespan of modified cells.…”

Section: Selection Of Gene Functions To Confer Resistance To Hivmentioning

confidence: 99%

Hematopoietic-Stem-Cell-Based Gene Therapy for HIV Disease

et al. 2012

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Although combination antiretroviral therapy can dramatically reduce the circulating viral load in those infected with HIV, replication-competent virus persists. To eliminate the need for indefinite treatment, there is growing interest in creating a functional HIV-resistant immune system through the use of gene-modified hematopoietic stem cells (HSC). Proof-of-concept for this approach has been provided in the instance of an HIV-infected adult transplanted with allogeneic stem cells from a donor lacking the HIV co-receptor, CCR5. Here, we review this and other strategies for HSC-based gene therapy for HIV disease.

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Stem cells, ribozymes and HIV

Cited by 9 publications

References 10 publications

RNA-Based Therapeutics: Current Progress and Future Prospects

RNA-Based Therapeutics: Current Progress and Future Prospects

Current progress of siRNA/shRNA therapeutics in clinical trials

Hematopoietic-Stem-Cell-Based Gene Therapy for HIV Disease

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