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Published on: January 30, 2019
Running interference: prospects and obstacles to using small interfering RNAs as small molecule drugs
Derek M Dykxhoorn1, Judy Lieberman
1CBR Institute for Biomedical Research, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. dykxhoor@cbr.med.harvard.edu
Annual Review of Biomedical Engineering
|July 13, 2006
Summary
RNA interference (RNAi) utilizes small interfering RNAs (siRNAs) to silence specific genes, offering therapeutic potential. However, effectively delivering siRNAs in vivo remains a key challenge for their use as drugs.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- RNA interference (RNAi) is a natural cellular process using small noncoding RNAs to regulate gene expression.
- Endogenous microRNAs are derived from hairpin precursors and control genes vital for cell death, differentiation, and development.
- RNAi also serves as a defense mechanism against viruses and transposons.
Purpose of the Study:
- To review recent advancements in utilizing small interfering RNAs (siRNAs) for therapeutic applications.
- To discuss the challenges and progress in overcoming obstacles for in vivo siRNA delivery.
- To explore the potential of siRNAs as small molecule drugs.
Main Methods:
- Review of current literature on RNA interference mechanisms and applications.
- Analysis of progress in siRNA-based gene silencing techniques.
- Examination of clinical studies and drug development hurdles for siRNA therapeutics.
Main Results:
- siRNAs can be introduced into cells to specifically silence target messenger RNAs (mRNAs) via the RNAi machinery.
- The technique is applicable to any disease-causing gene across various cell types and tissues.
- Early-stage clinical trials using siRNAs have commenced, indicating therapeutic promise.
Conclusions:
- RNA interference offers a powerful tool for gene-function analysis and drug discovery.
- siRNA-based therapies hold significant promise but face challenges in efficient in vivo delivery.
- Further research is needed to optimize siRNA delivery for successful therapeutic applications.
Related Concept Videos
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
01:23RNA Interference
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
02:30Small interfering RNAs (siRNA)
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
01:22MicroRNAs
MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...