By a News Reporter-Staff News Editor at Pharma Business Week -- From Alexandria, Virginia, NewsRx journalists report that a patent by the inventors Boday, Dylan J. (Austin, TX); Garcia, Jeannette M. (San Leandro, CA); Hedrick, James L. (Pleasanton, CA); Wojtecki, Rudy J. (San Jose, CA), filed on June 3, 2016, was published online on July 3, 2018 (see also International Business Machines Corporation).
The patent's assignee for patent number 10010627 is International Business Machines Corporation (Armonk, NY).
News editors obtained the following quote from the background information supplied by the inventors: "The present disclosure relates to modified polycationic polymeric materials and methods of modifying polycationic polymeric materials such as modified polyethylenimines having possible uses in gene or drug delivery, flocculating agents, or membranes, amongst others.
"Polyethylenimines (also sometimes referred to as poly(ethylenimine), poly(iminoethylene), polyaziridine, and poly[imino(1,2-ethanediyl)]) are polycationic polymeric materials which, among many other uses, have been investigated as transfection agents in gene therapy applications. That is, polyethylenimines have been investigated as a possible delivery vehicle for genetic material payloads (e.g., DNA and RNA) to be incorporated (transfected) into targeted cells for therapeutic purposes. Other possible uses of polyethylenimines are found in detergents, adhesives, water treatment, and paper making.
"Polycationic polymers in general, and polyethylenimines in particular, have been widely studied as polymeric gene delivery vehicles for use in gene therapy applications. That is, these polycationic materials have been investigated as means for protecting genetic material payloads (e.g., DNA and RNA) from enzymatic degradation and the like during transport through the body to targeted cells or tissue. Polyethylenimines are known to form polyplexes or polycondensates with genetic material due to electrostatic interactions between the amine groups of the polyethylenimine and phosphate groups in the nucleic acids making up the genetic material. Furthermore, materials with a polycationic character are considered to promote intake of the genetic material payload by target cells by promoting binding of polyplexes to the generally negatively charged cellular membrane. Once bound to the cellular membrane, the polyplex can pass into the interior of the cell by endocytosis. Once inside the cell, it still remains necessary for the genetic material to be released from the endosome into the cytoplasm and then reach the transcription mechanism inside the cell nucleus. Polyethylenimines provide a mechanism (the 'proton sponge effect') for rupturing the endosome and releasing the polyplex into the cytoplasm. Likewise the electrostatic nature of the binding between the polyethylenimine and the genetic material provides a means for releasing the genetic material into the cytoplasm for eventual diffusion into the nucleus. However, polyethylenimines are, in general, considered highly cytotoxic and, depending on molecular weight, may also be bioaccumulative. Since typical polyethylenimines are not readily biodegradable, in vivo accumulation is potentially problematic, especially given the known cytotoxicity.
"Furthermore, polyethylenimines, and polycationic gene delivery vehicles more broadly, are known to cause problems when the overall positive charging of the polyplex relative to complexed genetic material is increased. In general, polycationic-genetic material complexes are more easily incorporated into cellular targets than bare genetic material because the polycationic material shields/mitigates the inherent negative charges of the genetic material, which would otherwise cause the genetic material to be repulsed by the cellular membrane. The binding of the polyplex to the cellular membrane is generally improved with increased positive charge, and thus ultimately uptake of the polyplex by a target cell is improved by increasing positive charging of the polyplex. However, polyplexes with substantial overall positive charge may themselves require shielding while within the various transport pathways of the body. For example, without shielding the polyplexes may trigger unintended immune system responses and interactions with blood components (e.g., plasma proteins), which might cause premature removal of the polyplex and/or dangerous aggregation of components within the blood stream or tissue. In some instances, a polyplex core of a delivery vehicle may in turn be shielded using materials like polyethylene glycol (PEG) or polyacrylic acid. However, providing additional shielding for the polyplex in this manner will tend to reduce effectiveness with respect to target cell binding and the genetic payload's bioavailability once inside the target cell. As such, existing polymeric gene therapy delivery vehicles face issues regarding cytotoxicity, transfection efficiency, bioaccumulation, and/or unintended interactions during transport to cellular targets. Therefore, development of improved materials for polymeric gene delivery vehicles for gene therapy applications is desirable."
As a supplement to the background information on this patent, NewsRx correspondents also obtained the inventors' summary information for this patent: "According to one embodiment, a polymeric material comprising a polyethylenimine-based component including a group:
"##STR00002## wherein R1 includes a carbon atom and n is from 2 to 4. The group is attached to the polyethylenimine-based component at the end (wavy line) opposite the R1 end. In some embodiments, R1 can be an alkyl group, an aryl group, a polymeric group, an oligomeric group, a linkage to a polymeric group, or a linkage to an oligomeric group.
"According to another embodiment, a method of making a polymeric material includes contacting a polyethylenimine-based material corresponding to the following:
"##STR00003## and a cyclic phosphotriester corresponding to the following:
"##STR00004## wherein R1 includes a carbon atom, n is from 2 to 4, each instance of R2 is independently one of a hydrogen atom, a linear polyethylenimine segment, or a branched polyethylenimine segment, and m is such that a weight-average molecular weight (Mw) of the polyethylenimine-based material is between 100 Da to 10.sup.7 Da. In some embodiments, R1 can be an alkyl group, an aryl group, a polymeric group, an oligomeric group, a linkage to a polymeric group, or a linkage to an oligomeric group
"According to another embodiment, a method comprises complexing a genetic material and a polymeric material including a polyethylenimine-based component including having a group corresponding to the following:
"##STR00005## wherein R1 includes a carbon atom, and n is from 2 to 4. In some embodiments, R1 can be an alkyl group, an aryl group, a polymeric group, an oligomeric group, a linkage to a polymeric group, or a linkage to an oligomeric group."
For additional information on this patent, see: Boday, Dylan J.; Garcia, Jeannette M.; Hedrick, James L.; Wojtecki, Rudy J.. Modified Polycationic Polymers. U.S. Patent Number 10010627, filed June 3, 2016, and published online on July 3, 2018. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=10010627.PN.&OS=PN/10010627RS=PN/10010627
Keywords for this news article include: Biotechnology, Genetics, Cytoplasm, Gene Therapy, Bioengineering, Computer Companies, Drugs and Therapies, Intracellular Space, Technology Companies, International Business Machines Corporation.
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