Nucleic acid engineering

Mindblowingly cool design of riboswitches, nucleic acid logic circuits, etc.

This page mostly focuses on deliberate attempts to imitate electronic circuit design, and is obviously waaaay incomplete; I haven't even scratched the surface, really. It's strongest for logic gates and suchlike, and very weak on applications and on the chemical diversity of RNA. I haven't even gone near DNA nanotech. (go start a page!)

Literature

...currently a very incomplete list... please add/update!

Logic gates

• Automatic Design of Digital Synthetic Gene Circuits (Marchisio & Stelling)

• Enzyme-Free Nucleic Acid Logic Circuits (Seelig, Winfree et al)
  • DNA logic gates with no catalysis required -- everything is done by binding and conformational changes.

• Winfree: a bistable circuit using T7 polymerase and E.coli ribonuclease
  • http://www.nature.com/msb/journal/v2/n1/full/msb4100099.html

• Penchovsky R, Breaker RR.  Computational design and experimental validation of oligonucleotide-sensing allosteric ribozymes.  Nat Biotechnol. 2005 Nov;23(11):1424-33. Epub 2005 Oct 23.
  • One-shot YES,NOT,AND,OR gates using hammerhead ribozyme
  • in silico design pipeline using VIENNA
    • RNAfold, RNAinverse, RNAheat, kinRNA

• Rinaudo K, Bleris L, Maddamsetti R, Subramanian S, Weiss R, Benenson Y.  A universal RNAi-based logic evaluator that operates in mammalian cells.  Nat Biotechnol. 2007 Jul;25(7):795-801. Epub 2007 May 21.
  • RNAi logic

• Automated design and programming of a microfluidic DNA computer. M.S. Livstone, R. Weiss & L.F. Landweber. Natural Computing (2006), 5:1-13.
  • uses attached heating elements to control DNA annealing

• Rodrigo G, Landrain TE, Jaramillo A.  De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells.  Proc Natl Acad Sci U S A. 2012 Sep 18;109(38):15271-6. Epub 2012 Sep 4.
  • an evolutionary algorithm

• Auslander S, Auslander D, Muller M, Wieland M, Fussenegger M.  Programmable single-cell mammalian biocomputers.  Nature. 2012 Jul 5;487(7405):123-7. doi: 10.1038/nature11149.
  • not just nucleic acids (transcription factors involved too)

Energy

• Seelig G, Yurke B, Winfree E.  Catalyzed relaxation of a metastable DNA fuel.  J Am Chem Soc. 2006 Sep 20;128(37):12211-20.
  • Powering nucleic acid devices with DNA

I/O

• Stojanovic MN, Kolpashchikov DM.  Modular aptameric sensors.  J Am Chem Soc. 2004 Aug 4;126(30):9266-70.
  • noncovalent attachment to fluorophore

• Bayer TS, Smolke CD.  Programmable ligand-controlled riboregulators of eukaryotic gene expression.  Nat Biotechnol. 2005 Mar;23(3):337-43. Epub 2005 Feb 20.
  • ligand-gated riboswitches, GFP reporter

• Cheah MT, Wachter A, Sudarsan N, Breaker RR.  Control of alternative RNA splicing and gene expression by eukaryotic riboswitches.  Nature. 2007 May 24;447(7143):497-500. Epub 2007 Apr 29.
  • riboswitches in eukaryotes

Need more on aptamers here..

Ethics

• Cello J, Paul AV, Wimmer E.  Chemical synthesis of poliovirus cDNA: generation of infectious virus in the absence of natural template.  Science. 2002 Aug 9;297(5583):1016-8. Epub 2002 Jul 11.
  • total synthesis of poliovirus
  • ethical implications of this? my grandparents were killed by polio. discuss: what is the justification for building this thing?
  • some discussion at FAS
  • more in this article in the Indian Journal of Medical Ethics
  • apparently it was funded by the military
  • Craig Venter: "I think it's inflammatory without scientific justification. To purposely make a synthetic human pathogen is irresponsible."

Design principles, reviews

• Dirks RM, Lin M, Winfree E, Pierce NA.  Paradigms for computational nucleic acid design.  Nucleic Acids Res. 2004 Feb 27;32(4):1392-403. Print 2004.
  • rational design principles

• Isaacs FJ, Dwyer DJ, Collins JJ.  RNA synthetic biology.  Nat Biotechnol. 2006 May;24(5):545-54.
  • review

Applications

Cancer therapy

• Adele Fielding: measles virus
  • Fielding AK.  Measles as a potential oncolytic virus.  Rev Med Virol. 2005 Mar-Apr;15(2):135-42.
  • Bucheit AD, Kumar S, Grote DM, Lin Y, von Messling V, Cattaneo RB, Fielding AK.  An oncolytic measles virus engineered to enter cells through the CD20 antigen.  Mol Ther. 2003 Jan;7(1):62-72.

• Journals
  • Cancer Gene Therapy

Gene therapy

• "Human Gene Therapy: Present and Future"
  • review from 1999

• Kimelman N, Pelled G, Helm GA, Huard J, Schwarz EM, Gazit D.  Review: gene- and stem cell-based therapeutics for bone regeneration and repair.  Tissue Eng. 2007 Jun;13(6):1135-50.
  • bone engineering

• Asif-Ullah M, Levesque M, Robichaud G, Perreault JP.  Development of ribozyme-based gene-inactivations; the example of the hepatitis delta virus ribozyme.  Curr Gene Ther. 2007 Jun;7(3):205-16.
  • designed ribozymes and gene therapy

• Jang JH, Lim KI, Schaffer DV.  Library selection and directed evolution approaches to engineering targeted viral vectors.  Biotechnol Bioeng. 2007 Oct 15;98(3):515-24.
  • directed evolution of viruses for gene therapy

• Journals
  • Gene Therapy (Nature group)
  • Current Gene Therapy (Bentham)
  • Human Gene Therapy (Liebert)
  • Molecular Therapy (Elsevier)

need more up-to-date stuff here... this is a huge field

Design tools

Nupack

http://www.nupack.org/

• Dirks RM, Pierce NA.  An algorithm for computing nucleic acid base-pairing probabilities including pseudoknots.  J Comput Chem. 2004 Jul 30;25(10):1295-304.
• Dirks RM, Lin M, Winfree E, Pierce NA.  Paradigms for computational nucleic acid design.  Nucleic Acids Res. 2004 Feb 27;32(4):1392-403. Print 2004.

Vienna

http://www.tbi.univie.ac.at/~ivo/RNA/

• Hofacker IL.  Vienna RNA secondary structure server.  Nucleic Acids Res. 2003 Jul 1;31(13):3429-31.

Sribo

http://sfold.wadsworth.org/sribo.pl

• Ding Y, Chan CY, Lawrence CE.  Sfold web server for statistical folding and rational design of nucleic acids.  Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W135-41.

RNA-SSD

http://www.rnasoft.ca

• Andronescu M, Fejes AP, Hutter F, Hoos HH, Condon A.  A new algorithm for RNA secondary structure design.  J Mol Biol. 2004 Feb 20;336(3):607-24.

Sequence databases

• The Aptamer Database @ The Ellington Lab
• Rfam, Cambridge UK or WashU St Louis

Related pages on this wiki

• JournalClub