Home | Site Map | Contact
You are here: Home » Short RNA

Short RNA

and its Applications in Gene Silencing - PBL's Intellectual Property on Short RNA - Tech ID 99.190

Gene Silencing is a natural phenomenon that occurs in many different organisms from yeasts to plants to humans. It is a central biological mechanism for modulation of gene expression. David Baulcombe and Andrew Hamilton made the pioneering breakthrough to identify short (about 20-30 nucleotides) RNA molecules as the agents which both signal the occurrence of and induce gene silencing.  This ground breaking research was carried out at The Sainsbury Laboratory and published in Science ("A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants", Science (1999), 286, pp. 950-952).  Intellectual property rights in this innovation are assigned to PBL, The Sainsbury Laboratory's IP management company, and PBL has successfully filed and prosecuted patent applications for this technology since 1999. 

Professor Sir David Baulcombe is now at The University of Cambridge and Dr Andrew Hamilton is at The University of Glasgow. 
 

Induction of Gene Silencing

The use of short RNA molecules to induce gene silencing in organisms holds great promise as a therapeutic tool. Currently "gene therapy" applications are being developed for ailments as diverse as cancer, viral diseases and obesity. The technology is also referred to as "RNAi", short for RNA interference. 

The USPTO has now awarded to PBL a total of seven patents relating to the induction of gene silencing.  The first patent, US 8,097,710 for methods of inducing gene silencing using short RNA molecules and DNA constructs which produce such short RNA molecules, was issued on 17 January 2012.

Please click here for a PDF of the Press Release.

Subsequently, US Patent No. 8,258,285, US Patent No. 8,263,569 and US Patent No. 8,299,235 were issued on 4 September 2012, 11 September 2012 and 30 October 2012 respectively.  These new patents build on and extend the scope of claims previously conferred by US Patent No. 8,097,710 and now include methods involving RNAi molecules of 20 to 30 nucleotides as well as composition claims to the RNAi molecules themselves and constructs producing such RNAi molecules.

In addition to the broad method and composition claims granted during 2012, US Patent No. 8,349,607 is the first patent to extend the method claims into specific applications. The patent claims methods to silence target genes in a second cell or organism which is one of the major applications for the use of RNAi silencing in organisms. Now two other pending patent applications have been granted, US Patent No. 8,759,102 and US Patent No. 8,779,236 covering synthetic DNA constructs that express RNAi molecules and claims for silencing of targets in pests, parasites, predators or pathogens. 

Please click the links for PDFs of the press releases:  September 2012    October 2012    July 2014

In addition, PBL continues to prosecute several pending patent applications, based on further aspects of the work of Baulcombe and Hamilton. 

Detection of Gene Silencing

The use of short RNA molecules (including siRNA and miRNA) is an important tool to analyse miRNA expression patterns and to monitor siRNA levels following induction of silencing, for example, to determine whether experimental treatments or therapeutic interventions are having their intended effect on the expression of target genes such as those relevant to diseases, including cancer, macular degeneration etc. Such methods are widely and routinely used in biological research and related investigations.

Detection of Gene Silencing in Plants

In 2004, the United States Patent and Trademark Office (USPTO) awarded to PBL Patent No. 6,753,139, for methods of detecting gene silencing in plants.  Please click here for a link to the patent and claims.  PBL has granted licenses to several parties in respect of this patent, and additional licenses are still available. 

Detection of Gene Silencing In Mammals

In 2010, the USPTO awarded to PBL US Patent No. 7,704,688 (issue date 27 April 2010) with claims for detecting short RNA molecules to diagnose and characterise gene silencing in mammals and mammalian cells.  Please click here for a link to the claims.

Please click here for a PDF of the Press Release.

Licensing of Detection of Gene Silencing Patents

Commercial Use Licences under these issued patents are available for: 
•  Use in in-house research and development.
•  Use for performing Contract Research services to third parties.
•  Commercial supply of kits and/or reagents for performing the patented methods.
•  Use for confirming delivery of siRNA in clinical studies.

For licensing enquiries, please contact Dr Lars von Borcke.

Academic Use of Detection of Gene Silencing

PBL is operating a non-assert position under these issued detection of gene silencing patents with respect to academic organisations carrying out purely academic research, even if such purely academic research comes within the scope of the patent claims. By "purely academic research", is meant bona fide academic research or teaching carried out by public or charitable research institutions or universities and not performed for or under contract with any commercial entity or person. This non-assert position does not extend to use of commercial kits or reagents purchased by or donated to such public or charitable research organisations unless the supplier has already obtained a licence from PBL, under these patents, for such supply of such kits or reagents. 

Granted Patents

ISSUE DATE ISSUE NUMBER FIRST CLAIM
15 Jul 14 8,779,236 An isolated host cell of a host organism, said host cell modified to contain a DNA construct that expresses short antisense RNA molecules (SARMs) and short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and the SARMs consist of lengths of 20-30 nucleotides; wherein said SARMs are complementary to, and can base pair with, a target RNA, which target RNA is transcribed from a gene that is silenced when said SRMs are present in a cell of a pest, parasite, predator or pathogen of said host organism containing said gene, and said SSRMs correspond to the target RNA; and wherein said gene is endogenous to said pest, parasite, predator or pathogen of said host organism.
24 Jun 14 8,759,102 A cell comprising at least one synthetic DNA construct that expresses short antisense RNA molecules (SARMs) and short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and SARMs consist of 20-30 nucleotides, and wherein said SARMs are complementary to, and can base pair with, a target RNA in the cell, which target RNA is transcribed from a gene that is silenced when said SRMs are present in the cell, and said SSRMs correspond to the target RNA.
8 Jan 13 8,349,607 A method of silencing a target gene in a second cell or a second organism comprising introducing into said second cell or second organism, in which said target gene has not been silenced, either (a) a construct transcribable into short antisense RNA molecules (SARMs) and short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and SARMs consist of 20-30 nucleotides; wherein said SARMs have been identified as present in a first organism wherein the same gene has been silenced and said SARMs are complementary to, and can base pair with, target RNA transcribed from said gene that is silenced in said first organism, and said SSRMs correspond to the target RNA in said first organism; or (b) introducing said SRMs themselves into said second cell or second organism.
30 Oct 12 8,299,235 A composition for introduction into a cell to effect gene silencing, consisting essentially of isolated short antisense RNA molecules (SARMs) and isolated short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and the SARMs consist of 21-30 nucleotides; herein said SARMS are complementary to, and can base pair with, a target RNA, which target RNA is transcribed from a gene that is silenced when said SRMs are present in a cell containing said gene, and said SSRMs correspond to the target RNA; and wherein said gene is endogenous to an organism selected from the group consisting of a plant, a mammal, an avian organism, a reptile, an insect, and a protozoan, or said target RNA is generated by a pathogen.
11 Sep 12 8,263,569 A method of silencing a gene in cells which method comprises introducing into said cells a composition that consists essentially of isolated short antisense RNA molecules (SARMs) and isolated short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and SARMs consist of 20-30 nucleotides; wherein said SARMs are complementary to, and can base pair with, a target RNA, which target RNA is transcribed from a gene that is silenced when said SRMs are present in a cell containing said gene, and said SSRMs correspond to the target RNA; and wherein said gene is endogenous to an organism selected from the group consisting of a plant, a mammal, an avian organism, a reptile, an insect, and a protozoan, or said target RNA is generated by a pathogen, whereby said gene is silenced.
4 Sep 12 8,258,285 A composition for introduction into a cell to effect gene silencing, consisting essentially of isolated short antisense RNA molecules (SARMs) and isolated short sense RNA molecules (SSRMs), collectively short RNA molecules (SRMs), wherein the SSRMs and SARMs are each of a uniform length of 20-24 nucleotides; wherein said SARMs are complementary to and can base pair with a target RNA, which target RNA is transcribed from a gene that is silenced when said SRMs are present in a cell containing said gene, and said SSRMs correspond to the target RNA; wherein said gene is endogenous to an organism selected from the group consisting of a plant, a mammal, an avian organism, a reptile, an insect, and a protozoan, or said target RNA is generated by a pathogen; and wherein if said SARMs and SSRMs consist of 20 nucleotides, said SARMs and SSRMs are unmodified.
17 Jan 12 8,097,710 A method of silencing a gene in cells by post-transcriptional gene silencing (PTGS) which method comprises introducing into said cells a composition that contains short RNA molecules (SRMs), which SRMs are isolated short sense RNA molecules (SSRMs) and isolated short antisense RNA molecules (SARMs) at the same abundance; wherein said SARMs are complementary to a region of a target RNA transcribed from a gene which is silenced when said short RNA molecules are present in cells containing said gene and said SSRMs correspond to said target RNA; and wherein the SSRMs and SARMs consist of 20, 21, 22, 23 or 24 nucleotides, whereby said gene is silenced.
27 Apr 10 7,704,688 A method of detecting gene silencing of a target gene in a mammalian organism or in cellular material of a mammalian organism which method comprises the steps of: detecting in a nucleic acid extract prepared from said organism or in cellular material from said organism the presence as opposed to the absence of short RNA molecules (SRMs) of uniform length which are 20-30 nucleotides in length in said extract, characterizing any SRMs which are present in said extract wherein said characterizing comprises determining sequence identity or similarity with said target gene, wherein the presence of any SRMs having sequence identity or similarity with said target gene indicates silencing of said target gene in the organism or in cellular material from said organism, and confirming that said target gene has been silenced.
22 Jun 04 6,753,139 A method of detecting the silencing of a target gene in a plant, wherein said silencing is initiated by introduction of an exogenous nucleic acid, which method comprises the steps of: (i) obtaining a sample of material from said plant, (ii) producing a nucleic acid extract from said sample, (iii) analyzing said extract such as to determine the presence or absence of short RNA molecules which are 21-25 nucleotides in length (SRMs) in said extract, (iv) characterizing any SRMs which are present in said extract such as to determine sequence identity or similarity with said target gene, and (v) correlating the presence of said SRMs having sequence identity or similarity with said target gene in the extract with the occurrence of gene silencing in said plant.

 

Pending Patent Applications

USSN PUBLICATION NUMBER SUBJECT MATTER
14/332,138   RNAi molecules for 15 to 20 nucleotides.

 

Links and References

The Sainsbury Laboratory

The Lasker Foundation

A Species of Small Antisense RNA in Posttranscriptional Gene Silencing in Plants.  Hamilton, AJ, Baulcombe, DC.  Science (1999), 286, pp. 950-952.

Of maize and men, or peas and people: case histories to justify plants and other model systems.  David Baulcombe.  Commentary - Lasker Basic Medical Research Award.  Nature Medicine (2008) Volume 14, Number 10.

The perfect storm of tiny RNAs.  Gary Ruvkun.  Commentary - Lasker Basic Medical Research Award.  Nature Medicine (2008) Volume 14, Number 10.

The Evolution of our thinking about microRNAs.  Victor Ambros. Commentary - Lasker Basic Medical Research Award.  Nature Medicine (2008) Volume 14, Number 10.

Back to top