IP Library › Granted Patent US 12,264,344
Granted Patent B2
US 12,264,344 · App. 15/502,955 · Granted Apr 1, 2025

Protein/oligonucleotide core-shell nanoparticle therapeutics

Inventors: Chad A. Mirkin (Wilmette, IL); Jeffrey D. Brodin (Evanston, IL)
Assignee: Northwestern University
C12N9/2471A61K38/44A61K38/47A61K47/549A61K47/6921C07K19/00C12N9/0065C12N9/96C12P3/00C12P19/02C12P19/14C12Y111/01006C12Y302/01023B82Y5/00Y02P20/582
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,264,344
App. No.
15/502,955
Granted
Apr 1, 2025
Kind
B2
Abstract

The present disclosure is directed to core-shell nanoparticles, compositions comprising core-shell nanoparticles, and methods of their use.

Claims (49)

1. A method of inhibiting expression of a gene product encoded by a target polynucleotide comprising:

contacting a target polynucleotide with a nanoparticle comprising a core, a plurality of polynucleotides comprising a shell, and a linker,

wherein the linker connects the core to at least one polynucleotide of the plurality of polynucleotides comprising the shell and comprises:

Formula (I), (II), or both:

L and L 2 are each independently selected from C1-10 alkylene, —C(O)—C1-10 alkylene-Y— and —C(O)—C1-10 alkylene-Y—C1-10 alkylene-(OCH 2 CH 2 )m-Y—;

each Y is independently selected from the group consisting of a bond, C(O), O, NH, C(O)NH, and NHC(O);

m is 0, 1, 2, 3, 4, or 5; and

PN is the at least one polynucleotide of the plurality of polynucleotides comprising the shell,

wherein the core is a single protein,

wherein the single protein exhibits catalytic activity, the single protein does not exhibit transport activity and the single protein is not albumin,

wherein the plurality of polynucleotides comprising the shell are attached to the surface of the single protein via covalent bonds at a surface density of at least 10 pmol/cm 2 ,

wherein at least one polynucleotide of the plurality of polynucleotides comprising the shell is attached to the single protein surface via a surface amino group from a lysine residue of the single protein,

wherein at least one polynucleotide of the plurality of polynucleotides is sufficiently complementary to the target polynucleotide to hybridize under conditions sufficient to inhibit expression of the gene product by at least 10%, and

wherein at least one polynucleotide of the plurality of polynucleotides is 5 to 40 nucleotides in length.

2. The method of claim 1 , wherein the single protein is not a fragment.

3. The method of claim 1 , wherein at least one polynucleotide of the plurality of polynucleotides is 5 to 30 nucleotides in length.

4. The method of claim 1 , wherein the single protein is beta galactosidase or catalase.

5. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 15 pmol/cm 2 .

6. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 20 pmol/cm 2 .

7. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 25 pmol/cm 2 .

8. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 30 pmol/cm 2 .

9. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 35 pmol/cm 2 .

10. The method of claim 1 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 40 pmol/cm 2 .

11. The method of claim 1 , wherein expression of the gene product is inhibited by at least 10% compared to gene product expression in the absence of the nanoparticle.

12. A method of inhibiting expression of a gene product encoded by a target polynucleotide comprising:

contacting a target polynucleotide with a nanoparticle comprising a core a plurality of polynucleotides comprising a shell, and a linker,

wherein the linker connects the core to at least one polynucleotide of the plurality of polynucleotides comprising the shell and comprises:

Formula (I), (II), or both:

L and L 2 are each independently selected from C1-10 alkylene, —C(O)—C1-10 alkylene-Y—, and —C(O)—C1-10 alkylene-Y—C1-10 alkylene-(OCH 2 CH 2 )m-Y—;

each Y is independently selected from the group consisting of a bond, C(O), O, NH, C(O)NH, and NHC(O);

m is 0, 1, 2, 3, 4, or 5; and

PN is the at least one polynucleotide of the plurality of polynucleotides comprising the shell,

wherein the core is a single protein,

wherein the single protein:

(a) exhibits catalytic activity and exhibits therapeutic activity, but the single protein is not albumin, or

(b) exhibits catalytic activity and exhibits therapeutic activity, but the single protein is not a fragment,

wherein the plurality of polynucleotides comprising the shell are attached to the surface of the single protein via covalent bonds at a surface density of at least 10 pmol/cm 2 ,

wherein at least one polynucleotide of the plurality of polynucleotides comprising the shell is attached to the single protein surface via a surface amino group from a lysine residue of the single protein,

wherein at least one polynucleotide of the plurality of polynucleotides is sufficiently complementary to the target polynucleotide to hybridize under conditions sufficient to inhibit expression of the gene product by at least 10%, and

wherein at least one polynucleotide of the plurality of polynucleotides is 5 to 40 nucleotides in length.

13. The method of claim 12 , wherein at least one polynucleotide of the plurality of polynucleotides is 5 to 30 nucleotides in length.

14. The method of claim 12 , wherein each polynucleotide of the plurality of polynucleotides is 5 to 30 nucleotides in length.

15. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 15 pmol/cm 2 .

16. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 20 pmol/cm 2 .

17. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 25 pmol/cm 2 .

18. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 30 pmol/cm 2 .

19. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 35 pmol/cm 2 .

20. The method of claim 12 , wherein the shell attached to the surface of the single protein via covalent bonds are at a surface density of at least 40 pmol/cm 2 .

21. The method of claim 12 , wherein expression of the gene product is inhibited by at least 10% compared to gene product expression in the absence of the nanoparticle.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 26, 2017
From: MIRKIN, CHAD A.; BRODIN, JEFFREY D.
To: NORTHWESTERN UNIVERSITY
Reel/Frame 042517/0415 →
Continuity (4)
Provisional Application 62137183 · Mar 23, 2015
Provisional Application 62039608 · Aug 20, 2014
Provisional Application 62039340 · Aug 19, 2014
Related Publication 20170232109A1 · Aug 17, 2017
References Cited (400)
US 3687808A · Merigan, Jr. et al. · 1972 [cited by applicant]
US 4469863A · Ts'o et al. · 1984 [cited by applicant]
US 4476301A · Imbach et al. · 1984 [cited by applicant]
US 4489055A · Couvreur et al. · 1984 [cited by applicant]
US 4845205A · Huynh Dinh et al. · 1989 [cited by applicant]
US 4981957A · Lebleu et al. · 1991 [cited by applicant]
US 5008050A · Cullis et al. · 1991 [cited by applicant]
US 5023243A · Tullis · 1991 [cited by applicant]
US 5034506A · Summerton et al. · 1991 [cited by applicant]
US 5112963A · Pieles et al. · 1992 [cited by applicant]
US 5118800A · Smith et al. · 1992 [cited by applicant]
US 5130302A · Spielvogel et al. · 1992 [cited by applicant]
US 5134066A · Rogers et al. · 1992 [cited by applicant]
US 5166315A · Summerton et al. · 1992 [cited by applicant]
US 5175273A · Bischofberger et al. · 1992 [cited by applicant]
US 5177196A · Meyer, Jr. et al. · 1993 [cited by applicant]
US 5185444A · Summerton et al. · 1993 [cited by applicant]
US 5188897A · Suhadolnik et al. · 1993 [cited by applicant]
US 5194599A · Froehler et al. · 1993 [cited by applicant]
US 5214134A · Weis et al. · 1993 [cited by applicant]
US 5216141A · Benner · 1993 [cited by applicant]
US 5218105A · Cook et al. · 1993 [cited by applicant]
US 5235033A · Summerton et al. · 1993 [cited by applicant]
US 5245022A · Weis et al. · 1993 [cited by applicant]
US 5264423A · Cohen et al. · 1993 [cited by applicant]
US 5264562A · Matteucci · 1993 [cited by applicant]
US 5264564A · Matteucci · 1993 [cited by applicant]
US 5264618A · Felgner et al. · 1993 [cited by applicant]
US 5270163A · Gold et al. · 1993 [cited by applicant]
US 5276019A · Cohen et al. · 1994 [cited by applicant]
US 5278302A · Caruthers et al. · 1994 [cited by applicant]
US 5286717A · Cohen et al. · 1994 [cited by applicant]
US 5319080A · Leumann · 1994 [cited by applicant]
US 5321131A · Agrawal et al. · 1994 [cited by applicant]
US 5359044A · Cook et al. · 1994 [cited by applicant]
US 5367066A · Urdea et al. · 1994 [cited by applicant]
US 5393878A · Leumann · 1995 [cited by applicant]
US 5399676A · Froehler · 1995 [cited by applicant]
US 5405938A · Summerton et al. · 1995 [cited by applicant]
US 5405939A · Suhadolnik et al. · 1995 [cited by applicant]
US 5432272A · Benner · 1995 [cited by applicant]
US 5434257A · Matteucci et al. · 1995 [cited by applicant]
US 5446137A · Maag et al. · 1995 [cited by applicant]
US 5453496A · Caruthers et al. · 1995 [cited by applicant]
US 5455233A · Spielvogel et al. · 1995 [cited by applicant]
US 5457187A · Gmeiner et al. · 1995 [cited by applicant]
US 5459255A · Cook et al. · 1995 [cited by applicant]
US 5466677A · Baxter et al. · 1995 [cited by applicant]
US 5466786A · Buhr et al. · 1995 [cited by applicant]
US 5470967A · Huie et al. · 1995 [cited by applicant]
US 5476925A · Letsinger et al. · 1995 [cited by applicant]
US 5484908A · Froehler et al. · 1996 [cited by applicant]
US 5489677A · Sanghvi et al. · 1996 [cited by applicant]
US 5502177A · Matteucci et al. · 1996 [cited by applicant]
US 5514785A · Van Ness et al. · 1996 [cited by applicant]
US 5519126A · Hecht · 1996 [cited by applicant]
US 5519134A · Acevedo et al. · 1996 [cited by applicant]
US 5525711A · Hawkins et al. · 1996 [cited by applicant]
US 5527899A · Froehler · 1996 [cited by applicant]
US 5536821A · Agrawal et al. · 1996 [cited by applicant]
US 5539082A · Nielsen et al. · 1996 [cited by applicant]
US 5541306A · Agrawal et al. · 1996 [cited by applicant]
US 5541307A · Cook et al. · 1996 [cited by applicant]
US 5550111A · Suhadolnik et al. · 1996 [cited by applicant]
US 5552540A · Haralambidis · 1996 [cited by applicant]
US 5561225A · Maddry et al. · 1996 [cited by applicant]
US 5563253A · Agrawal et al. · 1996 [cited by applicant]
US 5565555A · Froehler et al. · 1996 [cited by applicant]
US 5567810A · Weis et al. · 1996 [cited by applicant]
US 5567811A · Misiura et al. · 1996 [cited by applicant]
US 5571799A · Tkachuk et al. · 1996 [cited by applicant]
US 5576427A · Cook et al. · 1996 [cited by applicant]
US 5587361A · Cook et al. · 1996 [cited by applicant]
US 5587469A · Cook et al. · 1996 [cited by applicant]
US 5591722A · Montgomery et al. · 1997 [cited by applicant]
US 5594121A · Froehler et al. · 1997 [cited by applicant]
US 5596086A · Matteucci et al. · 1997 [cited by applicant]
US 5596091A · Switzer · 1997 [cited by applicant]
US 5597909A · Urdea et al. · 1997 [cited by applicant]
US 5602240A · De Mesmaeker et al. · 1997 [cited by applicant]
US 5608046A · Cook et al. · 1997 [cited by applicant]
US 5610289A · Cook et al. · 1997 [cited by applicant]
US 5610300A · Altmann et al. · 1997 [cited by applicant]
US 5614617A · Cook et al. · 1997 [cited by applicant]
US 5618704A · Sanghvi et al. · 1997 [cited by applicant]
US 5623070A · Cook et al. · 1997 [cited by applicant]
US 5625050A · Beaton et al. · 1997 [cited by applicant]
US 5627053A · Usman et al. · 1997 [cited by applicant]
US 5633360A · Bischofberger et al. · 1997 [cited by applicant]
US 5637459A · Burke et al. · 1997 [cited by applicant]
US 5639873A · Barascut et al. · 1997 [cited by applicant]
US 5645985A · Froehler et al. · 1997 [cited by applicant]
US 5646265A · McGee · 1997 [cited by applicant]
US 5646269A · Matteucci et al. · 1997 [cited by applicant]
US 5658873A · Bertsch-Frank et al. · 1997 [cited by applicant]
US 5663312A · Chaturvedula · 1997 [cited by applicant]
US 5670633A · Cook et al. · 1997 [cited by applicant]
US 5672697A · Buhr et al. · 1997 [cited by applicant]
US 5677437A · Teng et al. · 1997 [cited by applicant]
US 5677439A · Weis et al. · 1997 [cited by applicant]
US 5681941A · Cook et al. · 1997 [cited by applicant]
US 5700920A · Altmann et al. · 1997 [cited by applicant]
US 5714331A · Buchardt et al. · 1998 [cited by applicant]
US 5719262A · Buchardt et al. · 1998 [cited by applicant]
US 5721218A · Froehler · 1998 [cited by applicant]
US 5750692A · Cook et al. · 1998 [cited by applicant]
US 5763588A · Matteucci et al. · 1998 [cited by applicant]
US 5792608A · Swaminathan et al. · 1998 [cited by applicant]
US 5792747A · Schally et al. · 1998 [cited by applicant]
US 5830653A · Froehler et al. · 1998 [cited by applicant]
US 6005096A · Matteucci et al. · 1999 [cited by applicant]
US 6051698A · Janjic et al. · 2000 [cited by applicant]
US 6080580A · Baker et al. · 2000 [cited by applicant]
US 6228642B1 · Baker et al. · 2001 [cited by applicant]
US 6287860B1 · Monia et al. · 2001 [cited by applicant]
US 6361944B1 · Mirkin et al. · 2002 [cited by applicant]
US 6506564B1 · Mirkin et al. · 2003 [cited by applicant]
US 6677153B2 · Iversen · 2004 [cited by applicant]
US 6942972B2 · Farooqui · 2005 [cited by examiner]
US 7048949B2 · Sligar et al. · 2006 [cited by applicant]
US 7223833B1 · Nielsen et al. · 2007 [cited by applicant]
US 7332586B2 · Franzen et al. · 2008 [cited by applicant]
US 7404969B2 · Chen et al. · 2008 [cited by applicant]
US 7514099B2 · Chen et al. · 2009 [cited by applicant]
US 7563618B2 · Gryaznov et al. · 2009 [cited by applicant]
US 7611728B2 · Kidane et al. · 2009 [cited by applicant]
US 7667004B2 · Zhong et al. · 2010 [cited by applicant]
US 7833992B2 · Vargeese et al. · 2010 [cited by applicant]
US 7956176B2 · McSwiggen et al. · 2011 [cited by applicant]
US 7964578B2 · Vargeese et al. · 2011 [cited by applicant]
US 8323686B2 · Mirkin et al. · 2012 [cited by applicant]
US 8431544B1 · Agrawal et al. · 2013 [cited by applicant]
US 8507200B2 · Mirkin et al. · 2013 [cited by applicant]
US 9139827B2 · Mirkin et al. · 2015 [cited by applicant]
US 9364443B2 · Beduneau et al. · 2016 [cited by applicant]
US 9506056B2 · Mirkin et al. · 2016 [cited by applicant]
US 9532948B2 · Mirkin et al. · 2017 [cited by applicant]
US 9549901B2 · Shi et al. · 2017 [cited by applicant]
US 9580708B2 · Uhlmann et al. · 2017 [cited by applicant]
US 9617541B2 · Mirkin et al. · 2017 [cited by applicant]
US 9844562B2 · Mirkin et al. · 2017 [cited by applicant]
US 9889209B2 · Mirkin et al. · 2018 [cited by applicant]
US 9902959B2 · Collard et al. · 2018 [cited by applicant]
US 10098958B2 · Mirkin et al. · 2018 [cited by applicant]
US 10182988B2 · Mirkin et al. · 2019 [cited by applicant]
US 10208310B2 · Mader et al. · 2019 [cited by applicant]
US 10370656B2 · Mirkin et al. · 2019 [cited by applicant]
US 10391116B2 · Mirkin et al. · 2019 [cited by applicant]
US 10398784B2 · Mirkin et al. · 2019 [cited by applicant]
US 10653780B2 · Hope et al. · 2020 [cited by applicant]
US 10792251B2 · Mirkin et al. · 2020 [cited by applicant]
US 20020172711A1 · Martin et al. · 2002 [cited by applicant]
US 20030022848A1 · Baker et al. · 2003 [cited by applicant]
US 20030147966A1 · Franzen et al. · 2003 [cited by applicant]
US 20030181412A1 · Erikson · 2003 [cited by applicant]
US 20040014956A1 · Woolf et al. · 2004 [cited by applicant]
US 20040023382A1 · Dean et al. · 2004 [cited by applicant]
US 20040158051A1 · Ozkan et al. · 2004 [cited by applicant]
US 20040219565A1 · Kauppinen et al. · 2004 [cited by applicant]
US 20050197315A1 · Taira et al. · 2005 [cited by applicant]
US 20050214782A1 · Chen et al. · 2005 [cited by applicant]
US 20050244858A1 · Rossi et al. · 2005 [cited by applicant]
US 20060008907A1 · Friedman et al. · 2006 [cited by applicant]
US 20060019917A1 · Guerciolini et al. · 2006 [cited by applicant]
US 20060025363A1 · Breitenbach et al. · 2006 [cited by applicant]
US 20060035344A1 · Pachuk et al. · 2006 [cited by applicant]
US 20060083781A1 · Shastri et al. · 2006 [cited by applicant]
US 20060148124A1 · Wilson · 2006 [cited by applicant]
US 20060252037A1 · Kolesnick et al. · 2006 [cited by applicant]
US 20060292174A1 · de los Rios et al. · 2006 [cited by applicant]
US 20070148251A1 · Hossainy et al. · 2007 [cited by applicant]
US 20080097092A1 · Khvorova et al. · 2008 [cited by applicant]
US 20080194463A1 · Weller et al. · 2008 [cited by applicant]
US 20080213177A1 · Rademacher et al. · 2008 [cited by applicant]
US 20080220072A1 · Unger et al. · 2008 [cited by applicant]
US 20080274454A1 · Mirkin et al. · 2008 [cited by applicant]
US 20080292545A1 · Lin et al. · 2008 [cited by applicant]
US 20080306016A1 · Mirkin et al. · 2008 [cited by applicant]
US 20080311182A1 · Ferrari et al. · 2008 [cited by applicant]
US 20090018028A1 · Lindsay et al. · 2009 [cited by applicant]
US 20090209629A1 · Mirkin et al. · 2009 [cited by applicant]
US 20090299045A1 · Richards et al. · 2009 [cited by applicant]
US 20090317802A1 · Bhatia et al. · 2009 [cited by applicant]
US 20090324706A1 · Mirkin et al. · 2009 [cited by applicant]
US 20100003317A1 · Akinc et al. · 2010 [cited by applicant]
US 20100092486A1 · Kandimalla et al. · 2010 [cited by applicant]
US 20100111968A1 · Branigan et al. · 2010 [cited by applicant]
US 20100136682A1 · Mirkin et al. · 2010 [cited by applicant]
US 20100184844A1 · Mirkin et al. · 2010 [cited by applicant]
US 20100233084A1 · Narasimhaswamy et al. · 2010 [cited by applicant]
US 20100233141A1 · Polach et al. · 2010 [cited by applicant]
US 20100233270A1 · Mirkin et al. · 2010 [cited by applicant]
US 20100310872A1 · Nakamura · 2010 [cited by applicant]
US 20110020242A1 · Zheng et al. · 2011 [cited by applicant]
US 20110111974A1 · Mirkin et al. · 2011 [cited by applicant]
US 20110223257A1 · Zhao et al. · 2011 [cited by applicant]
US 20110229529A1 · Irvine et al. · 2011 [cited by applicant]
US 20110244026A1 · Guild et al. · 2011 [cited by applicant]
US 20110256224A1 · Sigalov · 2011 [cited by applicant]
US 20110262347A1 · Ruoslahti · 2011 [cited by examiner]
US 20120244230A1 · Mirkin et al. · 2012 [cited by applicant]
US 20120282186A1 · Mirkin et al. · 2012 [cited by applicant]
US 20120288935A1 · Mirkin · 2012 [cited by examiner]
US 20130004520A1 · Andersson et al. · 2013 [cited by applicant]
US 20130034599A1 · Thaxton et al. · 2013 [cited by applicant]
US 20130123333A1 · Mirkin et al. · 2013 [cited by applicant]
US 20130136714A1 · Wang et al. · 2013 [cited by applicant]
US 20130178610A1 · Mirkin et al. · 2013 [cited by applicant]
US 20130295129A1 · Irvine et al. · 2013 [cited by applicant]
US 20130330839A1 · Suh et al. · 2013 [cited by applicant]
US 20140005258A1 · Mirkin et al. · 2014 [cited by applicant]
US 20140294927A1 · Thaxton et al. · 2014 [cited by applicant]
US 20160237429A1 · Cubillos-Ruiz et al. · 2016 [cited by applicant]
US 20160310425A1 · Mirkin et al. · 2016 [cited by applicant]
US 20170044544A1 · Mirkin · 2017 [cited by applicant]
US 20170130231A1 · Chae et al. · 2017 [cited by applicant]
US 20180200381A1 · Kannan · 2018 [cited by examiner]
US 20180344873A1 · Mirkin et al. · 2018 [cited by applicant]
US 20190030185A1 · Mirkin et al. · 2019 [cited by applicant]
US 20190275166A1 · Mirkin et al. · 2019 [cited by applicant]
US 20200022913A1 · Mirkin et al. · 2020 [cited by applicant]
US 20200101156A1 · Mirkin et al. · 2020 [cited by applicant]
US 20200291394A1 · Mirkin et al. · 2020 [cited by applicant]
CN 102165061A · 2011 [cited by applicant]
EP 1072679A2 · 2001 [cited by applicant]
EP 1889911A2 · 2008 [cited by applicant]
EP 2162117A2 · 2010 [cited by applicant]
EP 2366406A1 · 2011 [cited by applicant]
EP 2399608A1 · 2011 [cited by applicant]
WO WO1994001550A1 · 1994 [cited by applicant]
WO WO1995011910A1 · 1995 [cited by applicant]
WO WO9712896A1 · 1997 [cited by applicant]
WO WO1997012896A1 · 1997 [cited by applicant]
WO WO1998039352A1 · 1998 [cited by applicant]
WO WO1999014226A2 · 1999 [cited by applicant]
WO WO9927086A1 · 1999 [cited by applicant]
WO WO0020645A1 · 2000 [cited by applicant]
WO WO2002044321A2 · 2002 [cited by applicant]
WO WO2003008539A2 · 2003 [cited by applicant]
WO WO2003051278A2 · 2003 [cited by applicant]
WO WO2004047870A1 · 2004 [cited by applicant]
WO WO2005116226A2 · 2005 [cited by applicant]
WO WO2006088833A2 · 2006 [cited by applicant]
WO WO2006080946A2 · 2006 [cited by examiner]
WO WO2006138145A1 · 2006 [cited by applicant]
WO WO2007044851A2 · 2007 [cited by applicant]
WO WO2007047455A2 · 2007 [cited by applicant]
WO WO2007064857A2 · 2007 [cited by applicant]
WO WO2007089607A2 · 2007 [cited by applicant]
WO WO2007122405A1 · 2007 [cited by applicant]
WO WO200842156A1 · 2008 [cited by applicant]
WO WO2008098248A2 · 2008 [cited by applicant]
WO WO2008106660A2 · 2008 [cited by applicant]
WO WO2008127789A2 · 2008 [cited by applicant]
WO WO2008151049A2 · 2008 [cited by applicant]
WO WO2009012786A2 · 2009 [cited by applicant]
WO WO2009026412A1 · 2009 [cited by applicant]
WO WO200972657A1 · 2009 [cited by applicant]
WO WO2009105260A2 · 2009 [cited by applicant]
WO WO2009120887A2 · 2009 [cited by applicant]
WO WO2010017152A2 · 2010 [cited by applicant]
WO WO2010017154A2 · 2010 [cited by applicant]
WO WO2010060110A1 · 2010 [cited by applicant]
WO WO2010081049A1 · 2010 [cited by applicant]
WO WO2010081049A2 · 2010 [cited by applicant]
WO WO2010105209A1 · 2010 [cited by applicant]
WO WO2010120420A1 · 2010 [cited by applicant]
WO WO2010120420A2 · 2010 [cited by applicant]
WO WO2011017456A2 · 2011 [cited by applicant]
WO WO2011017690A2 · 2011 [cited by applicant]
WO WO2011053940A2 · 2011 [cited by applicant]
WO WO2011072133A1 · 2011 [cited by applicant]
WO WO2011079290A1 · 2011 [cited by applicant]
WO WO2011079290A2 · 2011 [cited by applicant]
WO WO2011113054A2 · 2011 [cited by applicant]
WO WO2011143608A1 · 2011 [cited by applicant]
WO WO2012055933A1 · 2012 [cited by applicant]
WO WO2012068470A2 · 2012 [cited by applicant]
WO WO2012170771A1 · 2012 [cited by applicant]
WO WO2013012628A2 · 2013 [cited by applicant]
WO WO2013016193A2 · 2013 [cited by applicant]
WO WO2013086207A1 · 2013 [cited by applicant]
WO WO2013177419A1 · 2013 [cited by applicant]
WO WO2014025795A1 · 2014 [cited by applicant]
WO WO2014123935A1 · 2014 [cited by applicant]
WO WO2014169264A2 · 2014 [cited by applicant]
WO WO2014172698A1 · 2014 [cited by applicant]
WO WO2015084884A2 · 2015 [cited by applicant]
WO WO2015195628A2 · 2015 [cited by applicant]
WO WO2016057549A1 · 2016 [cited by applicant]
WO WO2016115320A1 · 2016 [cited by applicant]
WO WO2017011662A1 · 2017 [cited by applicant]
WO WO2017035278A1 · 2017 [cited by applicant]
WO WO2018039629A2 · 2018 [cited by applicant]
WO WO2018138585A1 · 2018 [cited by applicant]
WO WO2018152327A2 · 2018 [cited by applicant]
WO WO2019118883A2 · 2019 [cited by applicant]
WO WO2019243430A1 · 2019 [cited by applicant]
Shukla et al., Development of Streptavidin-Based Nanocomplex for siRNA Delivery. Mol. Pharmaceutics 2013, 10, 4534-4545 (Year: 2013). [cited by examiner]
Lohcharoenkal et al., Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy. vol. 2014, Article ID 180549, 12 pages (Year: 2014). [cited by examiner]
KeraFast. Chemoselective Ligation through Copper-free Click Chemistry. Sep. 21, 2012, pp. 1-2, published on-line at http://www.kerafast.com/PDF/Chemoselective_Ligation_Sheet.pdf (Year: 2012). [cited by examiner]
Ming et al., Albumin-based Nanoconjugates for Targeted Delivery of Therapeutic Oligonucleotides. Biomaterials. Oct. 2013 ; 34(32):1-22 (Year: 2013). [cited by examiner]
Hotz et al., VEGF antisense therapy inhibits tumor growth and improves survival in experimental pancreatic cancer. Surgery 2005; 137:192-9 (Year: 2005). [cited by examiner]
Rajur et al., Covalent Protein-Oligonucleotide Conjugates for Efficient Delivery of Antisense Molecules. Bioconjugate Chem. 1997, 8, 935-940 (Year: 1997). [cited by examiner]
Poussin et al., Biochemical and functional analyses of gp130 mutants unveil JAK1 as a novel therapeutic target in human inflammatory hepatocellular adenoma. OncoImmunology 2:12, e27090; Dec. 2013; p. 1-8. (Year: 2013). [cited by examiner]
Duellman et al., Functional roles of N-linked glycosylation of human matrix metalloproteinase 9. Traffic. Oct. 2015; 16(10): 1108-1126. (Year: 2015). [cited by examiner]
Takakura-Yamamoto et al., O-Glycosylated Species of Natural Human Tumor-Necrosis Factor-α. Euro J. Biochem, 1996, 235:431-437. (Year: 1996). [cited by examiner]
Lin et al. Site-Specific Bioconjugation of a Murine Dihydrofolate Reductase Enzyme by Copper(I)-Catalyzed Azide-Alkyne Cycloaddition with Retained Activity (PLOS One, 2014, 9(6):e98403, pp. 1-10) (Year: 2014). [cited by examiner]
Gosh et al. Use of Maleimide-thiol coupling chemistry for efficient syntheses of oligonucleotide-enzyme conjugate hybridization probe (Bioconjugate Chem, 1990, 1:71-76) (Year: 1990). [cited by examiner]
Stevens et al. Chemical modification of enzymes: Critical evaluation of the graphical correlation between residual enzyme activity and number of groups modified. Bulletin Math Bio, 1980, 42:239-255. (Year: 1980). [cited by examiner]
Murakami et al., Highly sensitive detection of DNA using enzyme-linked DNA-probe. 1. Colorimetric and fluorometric detection (NAR, 1989, 17:5587-5595) (Year: 1989). [cited by examiner]
Cho et al., “Immunostimulatory DNA-based vaccines induce cytotoxic lymphocyte activity by a T-helper cell-independent mechanism,” Nature Biotechnology 18:509-514 (2000). [cited by applicant]
Ahmadi et al., “Shape-Controlled Synthesis of Colloidal Platinum Nanoparticles,” Science 272:1924-1926 (1996). [cited by applicant]
Altschul et al., “Basic Local Alignment Search Tool,” [cited by applicant]
Auyeung et al., “DNA-mediated nanoparticle crystallization into Wulff polyhedral,” Nature 505(7481): 73-77 (2014). [cited by applicant]
Auyeung et al., “Synthetically programmable nanoparticle superlattices using a hollow three-dimensional spacer approach,” Nat Nanotechnol 7(1):24-28 (2012). [cited by applicant]
Auyeung et al., “Transitioning DNA-Engineered Nanoparticle Superlattices from Solution to the Solid State,” Adv Mater 24(38):5181-5186 (2012). [cited by applicant]
Bahnemann, “Mechanisms of Organic Transformations on Semiconductor Particles,” Photochemical Conversion and Storage of Solar Energy, 251-276 (1991). [cited by applicant]
Beers et al., “A Spectrophotometric Method for Measuring the Breakdown of Hydrogen Peroxide by Catalase,” J Biol Chem 195(1):133-140 (1952). [cited by applicant]
Brodin et al., “DNA-mediated engineering of multicomponent enzyme crystals,” Proceedings National Academy of Sciences PNAS, 112(15):4564-4569 (2015). [cited by applicant]
Brodin et al., “Metal-directed, chemictally-tunable assembly of one-, two- and three-dimensional crystalline protein arrays,” Nat Chem 4(5): 375-382 (2012). [cited by applicant]
Brus, “Quantum Crystallites and Nonlinear Optics,” Appl. Phys. A53:465-474 (1991). [cited by applicant]
Cigler et al., “DNA-controlled assembly of a NaTI lattice structure from gold and protein nanoparticles,” Nat Mater 9(11): 918-922 (2010). [cited by applicant]
Concise Encyclopedia of Polymer Science and Engineering, “Polynucleotides,” J. I. Kroschwitz Ed., John Wiley & Sons, pp. 858-859 (1990). [cited by applicant]
Cook, “Medicinal chemistry of antisense oligonucleotides—future opportunities,” Anti-Cancer Drug Design, 6:585-607 (1991). [cited by applicant]
Coyle et al., “DNA-Mediated Assembly of Protein Heterodimers on Membrane Surfaces,” J Am Chem Soc 135(13):5012-5016 (2013). [cited by applicant]
Crawford et al., “Peptide aptamers: Tools for biology and drug discovery,” Briefings in Functional Genomics and Proteomics, 2(1):72-79 (2003). [cited by applicant]
Curtis et al., “A Morphology-Selective Copper Organosol,” Angew. Chem. Int. Ed. Engl., 27: 1530-1533 (1988). [cited by applicant]
De Mesmaeker et. al., “Backbone modifications in oligonucleotides and peptide nucleic acid systems,” Current Opinion in Structural Biology, 5:343-355 (1995). [cited by applicant]
Dotan et al., “Self-Assembly of a Tetrahedral Lectin into Predesigned Diamondlike Protein Crystals,” Angew Chem Int Ed 38(16): 2363-2366 (1999). [cited by applicant]
Eckstein, Oligonucleotides and Analogues, 1st Ed. (Oxford University Press, New York) (1991). [cited by applicant]
Eltoukhy, et al., “Nucleic acid-mediated intracellular protein delivery by lipid-like nanoparticles,” Biomaterials 35(24):6454-6461 (2014). [cited by applicant]
Englisch et al., “Chemically Modified Oligonucleotides as Probes and Inhibitors,” Angewandte Chemie, International Edition, 30:613-722 (1991). [cited by applicant]
Enustun, et al. “Coagulation of Colloidal Gold,” J. Am. Chem. Soc. 85:3317-3328 (1963). [cited by applicant]
Fattal, et al., “Biodegradable polyalkylcyanoacrylate nanoparticles for the delivery of oligonucleotides,” J. Controlled Release 53:137-143 (1998). [cited by applicant]
Freier et al., “The ups and downs of nucleic acid duplex stability: structure-stability studies on chemically-modified DNA:RNA duplexes,” Nucleic Acids Research, 25:4429-4443 (1997). [cited by applicant]
Hames et al., Gene Probes 1 A Practical Approach, IRL Press, New York (1995). [cited by applicant]
Hayashi, “Ultrafine particles,” J. Vac. Sci. Technol., A5(4):1375-1384 (1987). [cited by applicant]
Hayashi, “Ultrafine particles,” Physics Today, pp. 44-51 (1987). [cited by applicant]
Hayat, M. A. (ed.) Colloidal Gold: Principles, Methods, and Applications (Academic Press, San Diego, 1991). [cited by applicant]
Henglein et al., “Absorption Spectrum and Some Chemical Reactions of Colloidal Platinum in Aqueous Solution,” J. Phys. Chem., 99:14129-14136 (1995). [cited by applicant]
Henglein, “Mechanism of Reactions on Colloidal Microelectrodes and Size Quantization Effects,” Topics in Curr. Chem., 143:113-180 (1988). [cited by applicant]
Henglein, “Small-Particle Research: Physicochemical Properties of Extremely Small Colloidal Metal and Semiconductor Particles,” Chem. Rev., 89:1861-1873 (1989). [cited by applicant]
Hill et al., “Controlling the Lattice Parameters of Gold Nanoparticle FCC Crystals with Duplex DNA Linkers,” Nano Lett 8(8): 2341-2344 (2008). [cited by applicant]
Hurst et al., “Maximizing DNA Loading on a Range of Gold Nanoparticle Sizes,” Anal Chem 78(24): 8313-8318 (2006). [cited by applicant]
International Search Report and Written Opinion from PCT/US15/45971 dated Nov. 25, 2015. [cited by applicant]
Katz, “The reversible reaction of sodium thymonucleate and mercuric chloride,” [cited by applicant]
King et al., “Accurate design of coassembling multi-component protein nanomaterials,” Nature 510(7503): 103-108 (2014). [cited by applicant]
King et al., “Computational design of self-assembling protein nanomaterials with atomic level accuracy,” Science 336(6085): 1171-1174 (2012). [cited by applicant]
Kopylov et al., “Combinatorial Chemistry of Nucleic Acids: SELEX,” Molecular Biology 34(6): 940-954 (2000). [cited by applicant]
Kopylov et al., “Combinatorial Chemistry of Nucleic Acids: SELEX,” Molekulyarnaya Biologiya, vol. 34(6):1097-1113 (2000). [cited by applicant]
Kostiainen et al., “Electrostatic assembly of binary nanoparticle superlattices using protein cages,” Nat Nanotechnol 8(1): 52-56 (2013). [cited by applicant]
Kosturko et al., “The Crystal and Molecular Structure of a 2:1 Complex of 1-Methylthymine-Mercury(II),” Biochemistry, 13:3949-3952 (1974). [cited by applicant]
Kukowska-Latallo et al., “Efficient transfer of genetic material into mammalian cells using Starburst polyamidoamine dendrimers,” Proc. Natl. Acad. Sci. USA 93:4897-4902 (1996). [cited by applicant]
Liljestrom et al., “Self-assembly and modular functionalization of three-dimensional crystals from oppositely charged proteins,” Nat Commun 5(4445) pp. 1-9 (2014). [cited by applicant]
Liu et al., “New poly(d-glucaramidoamine)s induce DNA nanoparticle formation and efficient gene delivery into mammalian cells,” [cited by applicant]
Macfarlane et al., “Establishing the Design Rules for DNA-Mediated Programmable Colloidal Crystallization,” Angew Chem Int Ed Engl 49(27): 4589-4592 (2010). [cited by applicant]
Macfarlane et al., “Nanoparticle Superlattice Engineering with DNA,” Science 334:204-208 (2011). [cited by applicant]
Macfarlane et al., “Nucleic Acid-Modified Nanostructures as Programmable Atom Equivalents: Forging a New Table of Elements,” Angew Chem Int Ed 52(22): 5688-5698 (2013). [cited by applicant]
Mann, “Life as a Nanoscale Phenomenon,” Angew Chem Int Ed 47(29): 5306-5320 (2008). [cited by applicant]
Marinakos et al., “Gold Nanoparticles as Templates for the Synthesis of Hollow Nanometer-Sized Conductive Polymer Capsules,” Adv. Mater. 11:34-37 (1999). [cited by applicant]
Marinakos et al., “Template Synthesis of One-Dimensional Au, Au-Poly)pyrrole), and Poly(pyrrole) Nanoparticle Arrays,” Chem. Mater. 10:1214-1219 (1998). [cited by applicant]
Martin et al., “A New Access to 2′O-Alkylated Ribonucleosides and Properties of 2′-O-Alkylated Oligoribonucleotides,” Helv. Chim. Acta, 78:486-504 (1995). [cited by applicant]
Massart, “Preparation of Aqueous Magnetic Liquids in Alkaline and Acidic Media,” IEEE Transactions on Magnetics, 17:1247-1248 (1981). [cited by applicant]
Matijevic et al., “Fine Particles Part II: Formation Mechanisms and Applications,” MRS Bulletin, pp. 16-47 (1990). [cited by applicant]
Mayer et al., Nucleic Acid and Peptide Aptamers: Methods and Protocols (Edited by Mayer, Humana Press) Methods in Molecular Biology (2009). [cited by applicant]
Mirkin et al., “A DNA-based method for rationally assembling nanoparticles into macroscopic materials,” Nature 382:607-609 (1996). [cited by applicant]
Mozzarelli et al., “Protein Function in the Crystal,” Annu Rev Bioph Biom 25:343-365 (1996). [cited by applicant]
Nielsen et al., “Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide,” Science, 254:1497-1500 (1991). [cited by applicant]
Nykypanchuk et al., “DNA-guided crystallization of colloidal nanoparticles,” Nature 451:549-552 (2008). [cited by applicant]
Olshavsky et al., “Organometallic Synthesis of GaAs Crystallites Exhibiting Quantum Confinement,” J. Am. Chem. Soc., 112:9438-9439 (1990). [cited by applicant]
Oohora et al., “Supramolecular assembling systems formed by heme-heme pocket interactions in hemoproteins,” Chem Commun 48(96):11714-11726 (2012). [cited by applicant]
Padilla et al., “Nanohedra: Using symmetry to design self assembling protein cages, layers, crystals, and filaments,” Proc Natl Acad Sci USA 98(5): 2217-2221 (2001). [cited by applicant]
Park et al., “DNA-programmable nanoparticle crystallization,” Nature 451: 553-556 (2008). [cited by applicant]
Remington's Pharmaceutical Sciences, 16th Edition (1980). [cited by applicant]
Ringler et al., “Self-Assembly of Proteins into Designed Networks,” Science 302(5642):106-109 (2003). [cited by applicant]
Rudiuk et al., “Enhancement and Modulation of Enzymatic Activity through Higher-Order Structural Changes of Giant DNA-Protein Multibranch Conjugates,” Angewandte Chemie International Edition, 51(51):12694-12698 (2012). [cited by applicant]
Rusling et al., “Functionalizing Designer DNA Crystals with a Triple-Helical Veneer,” Angew Chem Int Ed 53(15): 3979-3982 (2014). [cited by applicant]
Sakai et al., “Protein crystalline frameworks with controllable interpenetration directed by dual supramolecular interactions,” Nat Commun 5: 4634 (2014). [cited by applicant]
Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989). [cited by applicant]
Samejima et al., “Reconstitution of Acid-denatured Catalase,” J Biol Chem 238(10): 3256-3261 (1963). [cited by applicant]
Sanghvi, Chapter 15, Heterocyclic Base Modification in Nucleic Acids and Their Applications in Antisense Oligonucleotides, Antisense Research and Applications, pp. 289-302, Crooke, S. T. and Lebleu, B., ed., CRC Press (… [cited by applicant]
Schmid, G. (ed.) Clusters and Colloids (VCH, Weinheim) (1994). [cited by applicant]
Schuttelkopf et al., “PRODRG: a tool for high-throughput crystallography of protein-ligand complexes,” Acta Crystallogr D 60: 1355-1363 (2004). [cited by applicant]
Seeman, “An Overview of Structural DNA Nanotechnology,” Mol Biotechnol 37(3): 246-257 (2007). [cited by applicant]
Sinclair et al., “Generation of protein lattices by fusing proteins with matching rotational symmetry,” Nat Nanotechnol 6(9): 558-562 (2011). [cited by applicant]
Strable et al., “Natural Nanochemical Building Blocks: Icosahedral Virus Particles Organized by Attached Oligonucleotides,” Nano Lett 4(8): 1385-1389 (2004). [cited by applicant]
Stranges et al., “A comparison of successful and failed protein interface designs highlights the challenges of designing buried hydrogen bonds,” Protein Sci 22(1): 74-82 (2013). [cited by applicant]
Thomas, “The Interaction of HgCl2 with Sodium Thymonucleate,” J. Am. Chem. Soc., 76:6032-6034 (1954). [cited by applicant]
Tondelli et al., “Highly efficient cellular uptake of c-myb antisense oligonucleotides through specifically designed polymeric nanospheres,” Nucl. Acids Res. 26:5425-5431(1998). [cited by applicant]
Tuerk et al., “Systematic Evolution of Ligands by Exponential Enrichment: RNA Ligands to Bacteriophage T4 DNA Polymerase,” Science 249:505-510 (1990). [cited by applicant]
Uchida et al., “GaAs Nanocrystals Prepared in Quinoline,” J. Phys. Chem., 95:5382-5384 (1992). [cited by applicant]
Wang et al., “Hierarchical Assembly of Plasmonic Nanosctuctures Using Virus Capsid Scaffolds on DNA Origami Templates,” ACS Nano 8(8):7896-7904 (2014). [cited by applicant]
Wang et al., “Nanometer-sized Semiconductor Clusters: Materials Synthesis, Quantum Size Effects, and Photophysical Properties,” J. Phys. Chem., 95:525-532 (1991). [cited by applicant]
Weller, “Colloidal Semiconductor Q-Particles: Chemistry in the Transition Region Between Solid State and Molecules,” Angew. Chem. Int. Ed. Engl., 32:41-53 (1993). [cited by applicant]
Wilner et al., “Enzyme cascades activated on topologically programmed DNA scaffolds,” Nat Nanotechnol 4(4): 249-254 (2009). [cited by applicant]
Winfree et al., “Design and self-assembly of two-dimensional DNA crystals,” Nature 394(6693): 539-544 (1998). [cited by applicant]
Xiong et al., “Phase Behavior of Nanoparticles Assembled by DNA Linkers,” Phys Rev Lett 102(1): 015504 (2009). [cited by applicant]
Yamane et al., “On the complexing of desoxyribonucleic acid (DNA) by mercuric ion,” J. Am. Chem. Soc., 83:2599-2607 (1961). [cited by applicant]
Yan et al., “Aptamers and aptamer targeted delivery,” RNA Biol. 6(3) 316-320 (2009). [cited by applicant]