Funding, Deals & Partnerships: BIOLOGICS & MEDICAL DEVICES; BioMed e-Series; Medicine and Life Sciences Scientific Journal – http://PharmaceuticalIntelligence.com
RAbD is a new biotechnology company founded by Fox Chase Cancer Center investigators Gregory Adams, Ph.D., Matthew Robinson, Ph.D. and Roland Dunbrack, Ph.D. that is focused on the knowledge-based design of antibodies that bind to key functional, often highly conserved and difficult to target epitopes. We are using homology modeling, crystal structures, protein docking and design software and algorithms to drive combinatorial sampling of CDRs to computationally design new antibodies and then express, validate and perform further design in an iterative manner.Brian Smith, Ph.D., MBA is RAbD Biotech’s Business Development Lead.
The company using in silico design methods to design to produce novel antibodies and biomimetics. The company is developing a first in class biomimetic, RaD-003, for the treatment of ovarian cancer. Ovarian cancer is one of the most deadly of all women’s cancers, with very low 5 year survival rates. An expected 22,000 US women a year will be diagnosed and expected 16,000 will die every year. Cisplatin/paclitaxel therapy is only approved and effective chemotherapy for ovarian cancer yet resistance develops quickly and is common. RaD-003 targets the MISII receptor (Mullerian Inhibiting Substance Type II Receptor), which is expressed on ovarian cancer cells but not on normal ovarian epithelium.
The MISII receptor had been considered undruggable as
MIS is too expensive and difficult to produce
previous attempts to develop therapeutic antibodies ot MISIIR have proven difficult
Therefore, the company used their computational platform to produce a “first in class” chimeric biomimetic to more effectively target and activate MISIIR.
For more information about this meeting and the Mid-Atlantic Bioangels and 1st Pitch please see posting on this site
The field of DNA and RNA nanotechnologies are considered one of the most dynamic research areas in the field of drug delivery in molecular medicine. Both DNA and RNA have a wide aspect of medical application including: drug deliveries, for genetic immunization, for metabolite and nucleic acid detection, gene regulation, siRNA delivery for cancer treatment (I), and even analytical and therapeutic applications.
Seeman (6,7) pioneered the concept 30 years ago of using DNA as a material for creating nanostructures; this has led to an explosion of knowledge in the now well-established field of DNA nanotechnology. The unique properties in terms of free energy, folding, noncanonical base-pairing, base-stacking, in vivo transcription and processing that distinguish RNA from DNA provides sufficient rationale to regard RNA nanotechnology as its own technological discipline. Herein, we will discuss the advantages of DNA nanotechnology and it’s use in medicine.
So What is the rational of using DNA nanotechnology(3)?
Genetic studies – its application in various biological fields like biomedicine, cancer research, medical devices and genetic engineering.
Its unique properties of structural stability, programmability of sequences, and predictable self-assembly.
Structures made from DNA using the DNA-origami method (Rothemund, 2006)
Structural DNA nanotechnology rests on three pillars: [1] Hybridization; [2] Stably branched DNA; and [3] Convenient synthesis of designed sequences.
Hybridization
Hybridization. The self-association (self=assembly) of complementary nucleic acid molecules or parts of molecules, is implicit in all aspects of structural DNA nanotechnology. Individual motifs are formed by the hybridization of strands designed to produce particular topological species. A key aspect of hybridization is the use of sticky ended cohesion to combine pieces of linear duplex DNA; this has been a fundamental component of genetic engineering for over 35 years (7). Not only is hybridization critical to the formation of structure, but it is deeply involved in almost all the sequence-dependent nanomechanical devices that have been constructed, and it is central to many attempts to build structural motifs in a sequential fashion (7,8 ).
Stably Branched DNA
branched DNA molecules are central to DNA nanotechnology. It is the combination of in vitro hybridization and synthetic branched DNA that leads to the ability to use DNA as a construction material. Such branched DNA is thought to be intermediates in genetic recombination (such as Holliday junctions).
Convenient Synthesis of Designed Sequences
Biologically derived branched DNA molecules, such as Holliday junctions, are inherently unstable, because they exhibit sequence symmetry; i.e., the four strands actually consist of two pairs of strands with the same sequence. This symmetry enables an isomerization known as branch migration that allows the branch point to relocate. DNA nanotechnology entailed sequence design that attempted to minimize sequence symmetry in every way possible.
One of the most remarkable innovations in structural DNA-nanotechnology in recent years is DNA origami, which was invented in 2006 by Paul Rothemund (1) (see Fig above). DNA origami utilizes the genome from a virus together with a large number of shorter DNA strands to enable the creation of numerous DNA-based structures (Figure 1). The shorter DNA strands forces the long viral DNA to fold into a pattern that is defined by the interaction between the long and the short DNA strands (1,2).
Rothemund believes that an application of patterned DNA origami would be the creation of a ‘nanobreadboard’, to which diverse components could be added. The attachment of proteins23, for example, might allow novel biological experiments aimed at modelling complex protein assemblies and examining the effects of spatial organization, whereas molecular electronic or plasmonic circuits might be created by attaching nanowires, carbon nanotubes or gold nanoparticles (1).
DNA nanotechnology and Biological Application
The physical and chemical properties of nanomaterials such as polymers, semiconductors, and metals present diverse advantages for various in vivo applications (3,9 ). For example:
Therapeutics – In cancer for example, nanosystems that are designed from biological materials such as DNA and RNA are ‘programmed’ to be able to evade most, if not all, drug-resistance mechanisms. Based on these properties, most nanosystems are able to deliver high concentrations of drugs to cancer cells while curtailing damage to surrounding healthy cells (2b, 3, 9, 11, 15).
Biosensors – capable of picking up very specific biological signals and converting them into electrical outputs that can be analyzed for identification. Biosensors are efficient as they have a high ratio of surface area to volume as well as adjustable electronic, magnetic, optical, and biological properties (3, 12, 13, 14).
**Amin and colleagues have developed a biotinylated DNA thin film-coated fiber optic reflectance biosensor for the detection of streptavidin aerosols. DNA thin films were prepared by dropping DNA samples into a polymer optical fiber which responded quickly to the specific biomolecules in the atmosphere. This approach of coating optical fibers with DNA nanostructures could be very useful in the future for detecting atmospheric bio-aerosols with high sensitivity and specificity (3, 14)
Computing – Another aspect uses the programmability of DNA to create devices that are capable of computing. Here, the structure of the assembled DNA is not of primary interest. Instead, control of the DNA sequence is used in the creation of computational algorithms, like e.g. artificial neural networks. Qian et al for example, built on the richness of DNA computing and strand displacement circuitry, they showed how molecular systems can exhibit autonomous brain-like behaviours. Using a simple DNA gate architecture that allows experimental scale-up of multilayer digital circuits, they systematically transform arbitrary linear threshold circuits (an artificial neural network model) into DNA strand displacement cascades that function as small neural networks (3, 10).
Additional features: 3rd generation DNA sequencers (II), Biomimetic systems, Energy transfer and photonics etc
Summary:
DNA nanotechnology is an evolving field that affects medicine, computation, material sciences, and physics. DNA nanostructures offer unprecedented control over shape, size, mechanical flexibility and anisotropic surface modification. Clearly, proper control over these aspects can increase circulation times by orders of magnitude, as can be seen for longcirculating particles such as erythrocytes and various pathogenic particles evolved to overcome this issue. The use of DNA in DNA/protein-based matrices makes these structures inherently amenable to structural tunability. More research in this direction will certainly be developed, making DNA a promising biomaterial in tissue engineering. future development of novel ways in which DNA would be utilized to have a much more comprehensive role in biological computation and data storage is envisaged.
3. Muniza Zahid, Byeonghoon Kim, Rafaqat Hussain, Rashid Amin and Sung H Park. DNA nanotechnology: a future perspective. Nanoscale Research Letters 2013, 8:119. http://www.nanoscalereslett.com/content/8/1/119
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