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GSJ: Received June 27 2005:
http://wbabin.net/saba/saba54.htm
Combinatorial Libraries of Beads, Viruses and/or Cells
James Saba
The use of beads in the synthesis and screening of libraries of molecules has been successful. Herein is described combinatorial libraries wherein each member is a different set of physically associated particles (including beads).
The figure below depicts the creation of a such a library, wherein we start with only two different beads of a primary library, each bead comprising a different covalently or noncovalently associated molecule (shown as black and gray); one or multiple identical oligonucleotides (exemplified as four thin lines); and optionally an encoding tag.
To these two bead library members we provide an excess of identical secondary beads, which comprise a unique molecule (shown as white) and one or multiple identical oligonucleotides complementary to those on the primary library members (exemplified as four thin lines). Consequent to mixing, complementary oligonucleotides hybridize to form different particle sets. These sets are then separated from nonbound secondary particles, which in this example is via magnetism.
One may stop at this point, or via a "split-and-mix" method synthesize more complex particle assembles, as the figure goes on to show.
"Particles" as defined herein also include capsules such as liposomes.
The oligonucleotides directing particle associations could be replaced with other types of association-specific molecules such as antibodies. Importantly, not only can such libraries be screened for affects of molecule combinations of molecules on a target such as a cell, but once such a combination is found, it or a derivative thereof can be used alone as an analytical tool or drug.
Furthermore, notice that other particles-like entities such as viruses and/or cells could be combined in a similar way. Such libraries are possible even without the use of supports, such as wherein the members express association proteins on their surface.
Lastly it is to be appreciated that such combinations can be assembled on a planar surface such as a biochip or cell surface.
While a provision US patent application has been filed on this invention, is at the conceptual stage and it is hoped that those with laboratories will investigate its full potential.
Provisional claims
2) The physically associated combination of different particles of claim 1, wherein the molecules are covalently affixed to the particles and have been synthesized in a combinatorial fashion.
3) A library particle combinations as described in claim 1 or 2, each member thereof comprising a unique set of different particles.
4) A physically associated combination of entities comprising viruses and/or cells, wherein physical assembly is effected by different protein association sequences engineered into the viruses and/or cells.
5) A library of different physically associated combinations of entities as described in claim 4.
6) A process for fabricating a library described by any claim above.
7) The process of claim 6, which incorporates a split-and-mix method.
8) A process for screening a library described by any claim above.
A one-bead, one-stock solution approach to chemical genetics: part 1 & 2 Blackwell, et al & Clemons, et al Chem Biol. 2001 Dec 8(12):1167-82 & 1183-95
Oligonucleotide tags for sorting and identification. Brenner, et al US Patent 5,846,719 Dec 8, 1998
Nucleic Acid Amplifications utilizing Polymers or Particles Conjugated with Multiple Primers. (See references therein) Saba, JA Gen Sci J 2005 June 24 http://wbabin.net/saba/saba52.htm
Supramolecular Constructs Comprising Addressable
DNA-conjugated Proteins Saba, JA Gen Sci J 2005 June
8 http://wbabin.net/saba/saba52.htm
Addendum 6/29/05
Similar combinatorial libraries can be constructed
using soluble linear or branched polymers rather than
beads, as exemplified in the figure below. A polymer
utilized, such as PEG, can be of any length and can
have one or more ligands conjugated, perhaps via a
cleavable linkage. As with beads specific associations
are preferably done via complementary oligos.
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It would be a great help if you could tell me if you have ever seen anything like what is described?