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A molecular processor is a processor that is based on a molecular^[1]^[2] platform rather than on an inorganic semiconductor in integrated circuit format.

Current technology

Molecular processors are currently in their infancy and currently only a few exist. At present a basic molecular processor is any biological or chemical system that uses a complementary DNA (cDNA) template to form a long chain amino acid molecule. A key factor that differentiates molecular processors is "the ability to control output" of protein or peptide concentration as a function of time. Simple formation of a molecule becomes the task of a chemical reaction, bioreactor or other polymerization technology. Current molecular processors take advantage of cellular processes to produce amino acid based proteins and peptides. The formation of a molecular processor currently involves integrating cDNA into the genome and should not replicate and re-insert, or be defined as a virus after insertion. Current molecular processors are replication incompetent, non-communicable and cannot be transmitted from cell to cell, animal to animal or human to human. All must have a method to terminate if implanted. The most effective methodology for insertion of cDNA (template with control mechanism) uses capsid technology to insert a payload into the genome. A viable molecular processor is one that dominates cellular function by re-task and or reassignment but does not terminate the cell. It will continuously produce protein or produce on demand and have method to regulate dosage if qualifying as a "drug delivery" molecular processor. Potential applications range from up-regulation of functional CFTR in cystic fibrosis and hemoglobin in sickle cell anemia to angiogenesis in cardiovascular stenosis to account for protein deficiency (used in gene therapy.)

Example

A vector inserted to form a molecular processor is described in part. The objective was to promote angiogenesis, blood vessel formation and improve cardiovasculature. Vascular endothelial growth factor (VEGF)^[3] and enhanced green fluorescent protein (EGFP) cDNA was ligated to either side of an internal ribosomal re-entry site (IRES) to produce inline production of both the VEGF and EGFP proteins. After in vitro insertion and quantification^[4] of integrating units (IUs), engineered cells produce a bioluminescent marker and a chemotactic growth factor. In this instance, increased fluorescence of EGFP is used to show VEGF production in individual cells with active molecular processors. The production was exponential in nature and regulated through use of an integrating promoter, cell numbers, the number of integrated units (IUs) of molecular processors and or cell numbers. The measure the molecular processors efficacy was performed by FC/FACS to indirectly measure VEGF through fluorescence intensity. Proof of functional molecular processing was quantified by ELISA to show VEGF effect through chemotactic and angiogenesis models. The result involved directed assembly and coordination of endothelial cells for tubule formation^[5] by engineered cells on endothelial cells. The research goes on to show implantation and VEGF with dosage capabilities to promote revascularization, validating mechanisms of molecular processor control.^[6]

References

^ Williams, Kevin Jon (2008). "Molecular processes that handle — and mishandle — dietary lipids". Journal of Clinical Investigation. 118 (10): 3247–59. doi:10.1172/JCI35206. PMC 2556568. PMID 18830418.
^ McBride, C; Gaupp, D; Phinney, DG (2003). "Quantifying levels of transplanted murine and human mesenchymal stem cells in vivo by real-time PCR". Cytotherapy. 5 (1): 7–18. doi:10.1080/14653240310000038. PMID 12745583.
^ Leung, D.; Cachianes, G; Kuang, W.; Goeddel, D.; Ferrara, N (1989). "Vascular endothelial growth factor is a secreted angiogenic mitogen". Science. 246 (4935): 1306–9. Bibcode:1989Sci...246.1306L. doi:10.1126/science.2479986. PMID 2479986.
^ Leutenegger, C; Klein, D; Hofmann-Lehmann, R; Mislin, C; Hummel, U; Böni, J; Boretti, F; Guenzburg, WH; Lutz, H (1999). "Rapid feline immunodeficiency virus provirus quantitation by polymerase chain reaction using the TaqMan fluorogenic real-time detection system". Journal of Virological Methods. 78 (1–2): 105–16. doi:10.1016/S0166-0934(98)00166-9. PMID 10204701.
^ Vernon, RB; Sage, EH (1999). "A novel, quantitative model for study of endothelial cell migration and sprout formation within three-dimensional collagen matrices". Microvascular Research. 57 (2): 118–33. doi:10.1006/mvre.1998.2122. PMID 10049660.
^ Russell Auger, PhD., Mesenchymal stromal cells as angiogenic cellular vectors for revascularizing the heart., 08.2006: PhD Thesis Publication available at Tulane University Library and through UMI Copyright 2006–2007.