From molecular biology to nanotechnology and nanomedicine.

Great progress in the development of molecular biology techniques has been seen since the discovery of the structure of deoxyribonucleic acid (DNA) and the implementation of a polymerase chain reaction (PCR) method. This started a new era of research on the structure of nucleic acids molecules, the development of new analytical tools, and DNA-based analyses. The latter included not only diagnostic procedures but also, for example, DNA-based computational approaches. On the other hand, people have started to be more interested in mimicking real life, and modeling the structures and organisms that already exist in nature for the further evaluation and insight into their behavior and evolution. These factors, among others, have led to the description of artificial organelles or cells, and the construction of nanoscale devices. These nanomachines and nanoobjects might soon find a practical implementation, especially in the field of medical research and diagnostics. The paper presents some examples, illustrating the progress in multidisciplinary research in the nanoscale area. It is focused especially on immunogenetics-related aspects and the wide usage of DNA molecules in various fields of science. In addition, some proposals for nanoparticles and nanoscale tools and their applications in medicine are reviewed and discussed.

[1]  S. Smith,et al.  Mechanical manipulation of single titin molecules with laser tweezers. , 2000, Advances in experimental medicine and biology.

[2]  P. Sado,et al.  Ophthalmic drug delivery systems—Recent advances , 1998, Progress in Retinal and Eye Research.

[3]  Masahiro Okamoto,et al.  Development of a System for the Inference of Large Scale Genetic Networks , 2000, Pacific Symposium on Biocomputing.

[4]  M. Schäfer-Korting,et al.  Vitamin A loaded solid lipid nanoparticles for topical use: occlusive properties and drug targeting to the upper skin. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[5]  D. Cunningham,et al.  Phase I clinical and pharmacokinetic study of bcl-2 antisense oligonucleotide therapy in patients with non-Hodgkin's lymphoma. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  B. Sabel,et al.  Nanoparticle technology for delivery of drugs across the blood-brain barrier. , 1998, Journal of pharmaceutical sciences.

[7]  J. Kreuter,et al.  Nanoparticulate systems for brain delivery of drugs. , 2001 .

[8]  E. Zanders,et al.  Gene expression analysis as an aid to the identification of drug targets. , 2000, Pharmacogenomics.

[9]  G. Russell-Jones Use of vitamin B12 conjugates to deliver protein drugs by the oral route. , 1998, Critical reviews in therapeutic drug carrier systems.

[10]  A. Ellington,et al.  Molecular computing: Does DNA compute? , 1996, Current Biology.

[11]  Hiroaki Kitano,et al.  Simulation of Genetic Interaction for Drosophila Leg Formation , 1998, Pacific Symposium on Biocomputing.

[12]  L J Kricka,et al.  Chip PCR. II. Investigation of different PCR amplification systems in microbabricated silicon-glass chips. , 1996, Nucleic acids research.

[13]  R. Mumper,et al.  Chitosan-based nanoparticles for topical genetic immunization. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[14]  J C Cox,et al.  The complexities of DNA computation. , 1999, Trends in biotechnology.

[15]  E B Baum,et al.  Building an associative memory vastly larger than the brain. , 1995, Science.

[16]  B. Cornell,et al.  A biosensor that uses ion-channel switches , 1997, Nature.

[17]  S. Jacobson,et al.  Multiple sample PCR amplification and electrophoretic analysis on a microchip. , 1998, Analytical chemistry.

[18]  S. Davis,et al.  Biomedical applications of nanotechnology--implications for drug targeting and gene therapy. , 1997, Trends in biotechnology.

[19]  Christopher G Thanos,et al.  Nanotechnology and medicine , 2003, Expert opinion on biological therapy.

[20]  David R. Forrest,et al.  Molecular nanotechnology , 2001 .

[21]  Christopher R. Lowe,et al.  Silicon microchambers for DNA amplification , 1998 .

[22]  Jorge Carneiro,et al.  Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications1 , 2001, The Journal of Immunology.

[23]  M. Highley,et al.  Nanotechnology in bio/clinical analysis. , 2000, Journal of chromatography. B, Biomedical sciences and applications.

[24]  Charles M. Lieber,et al.  Direct haplotyping of kilobase-size DNA using carbon nanotube probes , 2000, Nature Biotechnology.

[25]  G. Russell-Jones,et al.  Vitamin B12-mediated transport of nanoparticles across Caco-2 cells. , 1999, International journal of pharmaceutics.

[26]  D. Alpers,et al.  Vitamin B12 transporters. , 1999, Pharmaceutical biotechnology.

[27]  L F Landweber,et al.  Molecular computation: RNA solutions to chess problems , 2000, Proc. Natl. Acad. Sci. USA.

[28]  R. Mathies,et al.  Monolithic integrated microfluidic DNA amplification and capillary electrophoresis analysis system , 2000 .

[29]  P. Couvreur,et al.  Biodegradable polyalkylcyanoacrylate nanoparticles for the delivery of oligonucleotides. , 1998, Journal of controlled release : official journal of the Controlled Release Society.

[31]  G Rozenberg,et al.  Computing with DNA by operating on plasmids. , 2000, Bio Systems.

[32]  Shi V. Liu Debating controversies can enhance creativity , 2000, Nature.

[33]  L F Landweber,et al.  Chess games: a model for RNA based computation. , 1999, Bio Systems.

[34]  S. Boots Gel electrophoresis of DNA. , 1989, Analytical chemistry.

[35]  M. A. Northrup,et al.  A miniature analytical instrument for nucleic acids based on micromachined silicon reaction chambers. , 1998, Analytical chemistry.

[36]  Alan McClelland,et al.  Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector , 2000, Nature Genetics.

[37]  Kozo Kinoshita,et al.  Ligation errors in DNA computing. , 1999, Bio Systems.

[38]  J. Nemunaitis,et al.  A Phase I trial of h‐ras antisense oligonucleotide ISIS 2503 administered as a continuous intravenous infusion in patients with advanced carcinoma , 2001, Cancer.

[39]  V. Vlassov,et al.  Mechanism of oligonucleotide uptake by cells: involvement of specific receptors? , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[40]  YM Lo,et al.  On the potential of molecular computing. , 1995 .

[41]  G. M. Fahy Molecular nanotechnology : Return to the future , 1993 .

[42]  D. Treco,et al.  Nonviral transfer of the gene encoding coagulation factor VIII in patients with severe hemophilia A. , 2001, The New England journal of medicine.

[43]  K. Eric Drexler,et al.  Nanosystems - molecular machinery, manufacturing, and computation , 1992 .

[44]  C. G. Knight Liposomes, from physical structure to therapeutic applications , 1981 .

[45]  John S. McCaskill,et al.  Artificial Life VII: Proceedings of the Seventh International Conference on Artificial Life , 2000 .

[46]  T. Okano,et al.  Visualization of PEO-PBLA-Pyrene Polymeric Micelles by Atomic Force Microscopy , 1998, Pharmaceutical Research.

[47]  R J Lipton,et al.  DNA solution of hard computational problems. , 1995, Science.

[48]  J. Ulmer,et al.  Delivery Systems for Gene-based Vaccines , 2000, Molecular medicine.

[49]  A. Coutinho,et al.  A model of the immune network with B-T cell co-operation. I--Prototypical structures and dynamics. , 1996, Journal of theoretical biology.

[50]  Lloyd M. Smith,et al.  DNA computing on surfaces , 2000, Nature.

[51]  P. Couvreur,et al.  Development of a quantitative polyacrylamide gel electrophoresis analysis using a multichannel radioactivity counter for the evaluation of oligonucleotide-bound drug carrier. , 1996, Analytical biochemistry.

[52]  P. Couvreur,et al.  Liposome-entrapped ampicillin in the treatment of experimental murine listeriosis and salmonellosis , 1991, Antimicrobial Agents and Chemotherapy.

[53]  J. Hemmen,et al.  Cytokine-modulated regulation of helper T cell populations. , 2000, Journal of theoretical biology.

[54]  M. Alonso,et al.  Chitosan nanoparticles: a new vehicle for the improvement of the delivery of drugs to the ocular surface. Application to cyclosporin A. , 2001, International journal of pharmaceutics.

[55]  Piotr Wasiewicz,et al.  Adding numbers with DNA , 2000, Smc 2000 conference proceedings. 2000 ieee international conference on systems, man and cybernetics. 'cybernetics evolving to systems, humans, organizations, and their complex interactions' (cat. no.0.

[56]  K. Goodson,et al.  Transient liquid crystal thermometry of microfabricated PCR vessel arrays , 1998 .

[57]  J. Linderman,et al.  Mathematical modeling of helper T lymphocyte/antigen-presenting cell interactions: analysis of methods for modifying antigen processing and presentation. , 1996, Journal of theoretical biology.

[58]  A. Mountain,et al.  Gene therapy: the first decade. , 2000, Trends in biotechnology.

[59]  R R Breaker,et al.  Nucleic acid molecular switches. , 1999, Trends in biotechnology.

[60]  J. Alsner,et al.  An evolutionary-game model of tumour-cell interactions: possible relevance to gene therapy. , 2001, European journal of cancer.

[61]  N. Seeman,et al.  A nanomechanical device based on the B–Z transition of DNA , 1999, Nature.

[62]  D. A. Baxter,et al.  Modeling transcriptional control in gene networks—methods, recent results, and future directions , 2000, Bulletin of mathematical biology.

[63]  Mann A. Shoffner,et al.  Integrated cell isolation and polymerase chain reaction analysis using silicon microfilter chambers. , 1998, Analytical biochemistry.

[64]  N. Seeman DNA engineering and its application to nanotechnology. , 1999, Trends in biotechnology.

[65]  J. Collins,et al.  Construction of a genetic toggle switch in Escherichia coli , 2000, Nature.

[66]  F Guarnieri,et al.  Maya Blue Paint: An Ancient Nanostructured Material , 1996, Science.

[67]  B. Sleeman,et al.  Mathematical modeling of capillary formation and development in tumor angiogenesis: Penetration into the stroma , 2001 .

[68]  Masaru Tomita,et al.  E-CELL: software environment for whole-cell simulation , 1999, Bioinform..

[69]  S. Yoshioka,et al.  Is Stability Prediction Possible for Protein Drugs? Denaturation Kinetics of β- Galactosidase in Solution , 1994, Pharmaceutical Research.

[70]  J. Murray,et al.  A quantitative model for the dynamics of serum prostate-specific antigen as a marker for cancerous growth: an explanation for a medical anomaly. , 2001, The American journal of pathology.

[71]  Hao Yan,et al.  New motifs in DNA nanotechnology , 1998 .

[72]  D. A. Baxter,et al.  Mathematical Modeling of Gene Networks , 2000, Neuron.

[73]  Henry A. Erlich,et al.  Analysis of enzymatically amplified β-globin and HLA-DQα DNA with allele-specific oligonucleotide probes , 1986, Nature.

[74]  S G Grant,et al.  A mathematical model of in vitro cancer cell growth and treatment with the antimitotic agent curacin A. , 2001, Mathematical biosciences.

[75]  R. Freitas,et al.  Exploratory design in medical nanotechnology: a mechanical artificial red cell. , 1998, Artificial cells, blood substitutes, and immobilization biotechnology.

[76]  J. Vohradský Neural network model of gene expression , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[77]  C. Rudin,et al.  Phase I Trial of ISIS 5132, an antisense oligonucleotide inhibitor of c-raf-1, administered by 24-hour weekly infusion to patients with advanced cancer. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[78]  L M Adleman,et al.  Molecular computation of solutions to combinatorial problems. , 1994, Science.

[79]  D. Tang,et al.  DNA-based non-invasive vaccination onto the skin. , 1999, Vaccine.

[80]  M. Yamada,et al.  Successful peripheral T-lymphocyte-directed gene transfer for a patient with severe combined immune deficiency caused by adenosine deaminase deficiency. , 1998, Blood.

[81]  P. Couvreur,et al.  Design of folic acid-conjugated nanoparticles for drug targeting. , 2000, Journal of pharmaceutical sciences.

[82]  R. Müller,et al.  Solid lipid nanoparticles (SLN/Lipopearls)--a pharmaceutical and cosmetic carrier for the application of vitamin E in dermal products. , 1999, Journal of microencapsulation.

[83]  S. Davis,et al.  Chitosan as a novel nasal delivery system for vaccines. , 2001, Advanced drug delivery reviews.

[84]  David G. Messerschmitt The Future of Computer , 1996 .

[85]  Ravi Kumar M.N.V. Nano and microparticles as controlled drug delivery devices. , 2000 .

[86]  L. Neckers,et al.  Characterization of oligonucleotide transport into living cells. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[87]  D. Wood,et al.  Computation with biomolecules. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[88]  K. Mullis,et al.  Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. , 1986, Cold Spring Harbor symposia on quantitative biology.

[89]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[90]  M. A. Northrup,et al.  Functional integration of PCR amplification and capillary electrophoresis in a microfabricated DNA analysis device. , 1996, Analytical chemistry.

[91]  Theresa B. Taylor,et al.  Process Control for Optimal PCR Performance in Glass Microstructures , 1998 .

[92]  D. Dasgupta,et al.  A formal model of an artificial immune system. , 2000, Bio Systems.

[93]  A T woolley Biomedical microdevices and nanotechnology. , 2001, Trends in biotechnology.

[94]  T. Eng On solving 3CNF-satisfiability with an in vivo algorithm. , 1999, Bio Systems.

[95]  R. Langer,et al.  Biomaterials in drug delivery and tissue engineering: one laboratory's experience. , 2000, Accounts of chemical research.

[96]  Drexler Ke,et al.  Molecular engineering: An approach to the development of general capabilities for molecular manipulation. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[97]  A. Gewirtz Myb targeted therapeutics for the treatment of human malignancies , 1999, Oncogene.

[98]  G. Birrenbach,et al.  Polymerized micelles and their use as adjuvants in immunology. , 1976, Journal of pharmaceutical sciences.

[99]  A. R. Kulkarni,et al.  Biodegradable polymeric nanoparticles as drug delivery devices. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[100]  E. Yeung,et al.  Automated and integrated system for high-throughput DNA genotyping directly from blood. , 1999, Analytical chemistry.

[101]  T. Bettinger,et al.  Chitosan-Based Vector/DNA Complexes for Gene Delivery: Biophysical Characteristics and Transfection Ability , 1998, Pharmaceutical Research.

[102]  David J. Triggle,et al.  Pharmaceutical Sciences in the Next Millennium , 1999 .

[103]  P. Couvreur,et al.  Nanoparticulate systems for the delivery of antisense oligonucleotides. , 2001, Advanced drug delivery reviews.

[104]  P D Kaplan,et al.  DNA solution of the maximal clique problem. , 1997, Science.

[105]  T. A. Taton Nanotechnology: Boning up on biology , 2001, Nature.