(1) Ramamoorth, M.; Narvekar, A. Non Viral Vectors in Gene Therapy - An Overview. J. Clin. Diagnostic Res. 2015, 9 (1), GE01–GE06. https://doi.org/10.7860/JCDR/2015/10443.5394.
(2) Li, S. D.; Huang, L. Non-Viral Is Superior to Viral Gene Delivery. J. Control. Release 2007, 123 (3), 181–183. https://doi.org/10.1016/j.jconrel.2007.09.004.
(3) Trapani, I.; Tornabene, P.; Auricchio, A. Large Gene Delivery to the Retina with AAV Vectors: Are We There Yet? Gene Ther. 2021, 28 (5), 220–222. https://doi.org/10.1038/s41434-020-0174-4.
(4) May, M. Viral Vector Industry Boosts Product Quality and Quantity. Genet. Eng. Biotechnol. News 2020, 40 (3), 42–44, 46. https://doi.org/10.1089/gen.40.03.11.
(5) Nayak, S.; Herzog, R. W. Progress and Prospects: Immune Responses to Viral Vectors. Gene Ther. 2010, 17 (3), 295–304. https://doi.org/10.1038/gt.2009.148.
(6) Liu, C.; Zhang, L.; Liu, H.; Cheng, K. Delivery Strategies of the CRISPR-Cas9 Gene-Editing System for Therapeutic Applications. J. Control. Release 2017, 266 (September), 17–26. https://doi.org/10.1016/j.jconrel.2017.09.012.
(7) Kumar, R.; Santa Chalarca, C. F.; Bockman, M. R.; Bruggen, C. Van; Grimme, C. J.; Dalal, R. J.; Hanson, M. G.; Hexum, J. K.; Reineke, T. M. Polymeric Delivery of Therapeutic Nucleic Acids. Chem. Rev. 2021, 121 (18), 11527–11652. https://doi.org/10.1021/acs.chemrev.0c00997.
(8) Van Bruggen, C.; Hexum, J. K.; Tan, Z.; Dalal, R. J.; Reineke, T. M. Nonviral Gene Delivery with Cationic Glycopolymers. Acc. Chem. Res. 2019. https://doi.org/10.1021/acs.accounts.8b00665.
(9) Perrier, S. 50th Anniversary Perspective: RAFT Polymerization - A User Guide. Macromolecules 2017, 50 (19), 7433–7447. https://doi.org/10.1021/acs.macromol.7b00767.
(10) Chiefari, J.; Chong, Y. K. B.; Ercole, F.; Krstina, J.; Jeffery, J.; Le, T. P. T.; Mayadunne, R. T. A.; Meijs, G. F.; Moad, C. L.; Moad, G.; Rizzardo, E.; Thang, S. H.; South, C. Living Free-Radical Polymerization by Reversible Addition - Fragmentation Chain Transfer : The RAFT Process. Macromolecules 1998, 9297 (98), 5559–5562.
(11) Moad, G. RAFT Polymerization – Then and Now. 2015, 211–246. https://doi.org/10.1021/bk-2015-1187.ch012.
(12) Grubbs, R. B. Nitroxide-Mediated Radical Polymerization: Limitations and Versatility. Polym. Rev. 2011, 51 (2), 104–137. https://doi.org/10.1080/15583724.2011.566405.
(13) Hawker, C. J.; Bosman, A. W.; Harth, E. New Polymer Synthesis by Nitroxide Mediated Living Radical Polymerizations. Chem. Rev. 2001, 101 (12), 3661–3688. https://doi.org/10.1021/cr990119u.
(14) Matyjaszewski, K. Atom Transfer Radical Polymerization (ATRP): Current Status and Future Perspectives. Macromolecules 2012, 45 (10), 4015–4039. https://doi.org/10.1021/ma3001719.
(15) Matyjaszewski, K.; Xia, J. Atom Transfer Radical Polymerization. Chem. Rev. 2001, 101 (9), 2921–2990. https://doi.org/10.1021/cr940534g.
(16) Gibson, M. I.; Hlich, E. F.; Klok, H.-A. Postpolymerization Modification of Poly(Pentafluorophenyl Methacrylate): Synthesis of a Diverse Water-Soluble Polymer Library. Am. Chem. Soc. Polym. Prepr. Div. Polym. Chem. 2008, 49 (1), 511–512. https://doi.org/10.1002/pola.
(17) Santa Chalarca, C. F.; Dalal, R. J.; Chapa, A.; Hanson, M. G.; Reineke, T. M. Cation Bulk and p K a Modulate Diblock Polymer Micelle Binding to PDNA. ACS Macro Lett. 2022, 588–594. https://doi.org/10.1021/acsmacrolett.2c00015.
(18) Gauthier, M. A.; Gibson, M. I.; Klok, H.-A. Synthesis of Functional Polymers by Post-Polymerization Modification. Angew. Chemie Int. Ed. 2009, 48 (1), 48–58. https://doi.org/10.1002/anie.200801951.
(19) Akinc, A.; Lynn, D. M.; Anderson, D. G.; Langer, R. Parallel Synthesis and Biophysical Characterization of a Degradable Polymer Library for Gene Delivery. J. Am. Chem. Soc. 2003, 125 (18), 5316–5323. https://doi.org/10.1021/ja034429c.
(20) Barua, S.; Joshi, A.; Banerjee, A.; Matthews, D.; Sharfstein, S. T.; Cramer, S. M.; Kane, R. S.; Rege, K. Parallel Synthesis and Screening of Polymers for Nonviral Gene Delivery. Mol. Pharm. 2009, 6 (1), 86–97. https://doi.org/10.1021/mp800151j.
(21) Goldberg, M.; Mahon, K.; Anderson, D. Combinatorial and Rational Approaches to Polymer Synthesis for Medicine☆. Adv. Drug Deliv. Rev. 2008, 60 (9), 971–978. https://doi.org/10.1016/j.addr.2008.02.005.
(22) Anderson, D. G.; Akinc, A.; Hossain, N.; Langer, R. Structure/Property Studies of Polymeric Gene Delivery Using a Library of Poly(β-Amino Esters). Mol. Ther. 2005, 11 (3), 426–434. https://doi.org/10.1016/j.ymthe.2004.11.015.
(23) Kumar, R.; Le, N.; Oviedo, F.; Brown, M. E.; Reineke, T. M. Combinatorial Polycation Synthesis and Causal Machine Learning Reveal Divergent Polymer Design Rules for Effective PDNA and Ribonucleoprotein Delivery. JACS Au 2022, 2 (2), 428–442. https://doi.org/10.1021/jacsau.1c00467.
(24) Kumar, R.; Le, N.; Tan, Z.; Brown, M. E.; Jiang, S.; Reineke, T. M. Efficient Polymer-Mediated Delivery of Gene-Editing Ribonucleoprotein Payloads through Combinatorial Design, Parallelized Experimentation, and Machine Learning. ACS Nano 2020, 14 (12), 17626–17639. https://doi.org/10.1021/acsnano.0c08549.
(25) Patra, T. K. Data-Driven Methods for Accelerating Polymer Design. ACS Polym. Au 2022, 2 (1), 8–26. https://doi.org/10.1021/acspolymersau.1c00035.
(26) Batra, R.; Song, L.; Ramprasad, R. Emerging Materials Intelligence Ecosystems Propelled by Machine Learning. Nat. Rev. Mater. 2021, 6 (8), 655–678. https://doi.org/10.1038/s41578-020-00255-y.
(27) Upadhya, R.; Kosuri, S.; Tamasi, M.; Meyer, T. A.; Atta, S.; Webb, M. A.; Gormley, A. J. Automation and Data-Driven Design of Polymer Therapeutics. Adv. Drug Deliv. Rev. 2021, 171, 1–28. https://doi.org/10.1016/j.addr.2020.11.009.
(28) Gormley, A. J.; Webb, M. A. Machine Learning in Combinatorial Polymer Chemistry. Nat. Rev. Mater. 2021, 6 (8), 642–644. https://doi.org/10.1038/s41578-021-00282-3.
(29) Ramprasad, R.; Batra, R.; Pilania, G.; Mannodi-Kanakkithodi, A.; Kim, C. Machine Learning and Materials Informatics: Recent Applications and Prospects. npj Comput. Mater. 2017, 3 (1), 54. https://doi.org/10.1038/s41524-017-0056-5.
(30) Gómez-Bombarelli, R.; Aguilera-Iparraguirre, J.; Hirzel, T. D.; Duvenaud, D.; Maclaurin, D.; Blood-Forsythe, M. A.; Chae, H. S.; Einzinger, M.; Ha, D.-G.; Wu, T.; Markopoulos, G.; Jeon, S.; Kang, H.; Miyazaki, H.; Numata, M.; Kim, S.; Huang, W.; Hong, S. I.; Baldo, M.; Adams, R. P.; Aspuru-Guzik, A. Design of Efficient Molecular Organic Light-Emitting Diodes by a High-Throughput Virtual Screening and Experimental Approach. Nat. Mater. 2016, 15 (10), 1120–1127. https://doi.org/10.1038/nmat4717.
(31) Kumar, J. N.; Li, Q.; Tang, K. Y. T.; Buonassisi, T.; Gonzalez-Oyarce, A. L.; Ye, J. Machine Learning Enables Polymer Cloud-Point Engineering via Inverse Design. npj Comput. Mater. 2019, 5 (1), 73. https://doi.org/10.1038/s41524-019-0209-9.
(32) Wang, Y.; Xie, T.; France-Lanord, A.; Berkley, A.; Johnson, J. A.; Shao-Horn, Y.; Grossman, J. C. Toward Designing Highly Conductive Polymer Electrolytes by Machine Learning Assisted Coarse-Grained Molecular Dynamics. Chem. Mater. 2020, 32 (10), 4144–4151. https://doi.org/10.1021/acs.chemmater.9b04830.
(33) Tamasi, M. J.; Patel, R. A.; Borca, C. H.; Kosuri, S.; Mugnier, H.; Upadhya, R.; Murthy, N. S.; Webb, M. A.; Gormley, A. J. Machine Learning on a Robotic Platform for the Design of Polymer–Protein Hybrids. Adv. Mater. 2022, 2201809, 2201809. https://doi.org/10.1002/adma.202201809.
(34) Das, A.; Theato, P. Multifaceted Synthetic Route to Functional Polyacrylates by Transesterification of Poly(Pentafluorophenyl Acrylates). Macromolecules 2015, 48 (24), 8695–8707. https://doi.org/10.1021/acs.macromol.5b02293.
(35) Günay, K. A.; Schüwer, N.; Klok, H. A. Synthesis and Post-Polymerization Modification of Poly(Pentafluorophenyl Methacrylate) Brushes. Polym. Chem. 2012, 3 (8), 2186–2192. https://doi.org/10.1039/c2py20162c.
(36) Blasco, E.; Sims, M. B.; Goldmann, A. S.; Sumerlin, B. S.; Barner-Kowollik, C. 50th Anniversary Perspective: Polymer Functionalization. Macromolecules 2017, 50 (14), 5215–5252. https://doi.org/10.1021/acs.macromol.7b00465.
(37) Hoyle, C. E.; Bowman, C. N. Thiol-Ene Click Chemistry. Angew. Chemie - Int. Ed. 2010, 49 (9), 1540–1573. https://doi.org/10.1002/anie.200903924.
(38) Van Bruggen, C.; Punihaole, D.; Keith, A. R.; Schmitz, A. J.; Tolar, J.; Frontiera, R. R.; Reineke, T. M. Quinine Copolymer Reporters Promote Efficient Intracellular DNA Delivery and Illuminate a Protein-Induced Unpackaging Mechanism. Proc. Natl. Acad. Sci. 2020, 117 (52), 32919–32928. https://doi.org/10.1073/pnas.2016860117.
(39) Pezzoli, D.; Giupponi, E.; Mantovani, D.; Candiani, G. Size Matters for in Vitro Gene Delivery: Investigating the Relationships among Complexation Protocol, Transfection Medium, Size and Sedimentation. Sci. Rep. 2017, 7 (1), 44134. https://doi.org/10.1038/srep44134.
(40) Bhattacharya, S.; Chaudhuri, P. Medical Implications of Benzimidazole Derivatives as Drugs Designed for Targeting DNA and DNA Associated Processes. Curr. Med. Chem. 2008, 15 (18), 1762–1777. https://doi.org/10.2174/092986708785133013.
(41) Kubota, Y.; Iwamoto, T.; Seki, T. The Interaction of Benzimidazole Compounds with DNA: Intercalation and Groove Binding Modes. Nucleic Acids Symp. Ser. 1999, 42 (1), 53–54. https://doi.org/10.1093/nass/42.1.53.
(42) Shi, J.; Schellinger, J. G.; Johnson, R. N.; Choi, J. L.; Chou, B.; Anghel, E. L.; Pun, S. H. Influence of Histidine Incorporation on Buffer Capacity and Gene Transfection Efficiency of HPMA- Co -Oligolysine Brush Polymers. Biomacromolecules 2013, 14 (6), 1961–1970. https://doi.org/10.1021/bm400342f.
(43) Nelson, A. M.; Pekkanen, A. M.; Forsythe, N. L.; Herlihy, J. H.; Zhang, M.; Long, T. E. Synthesis of Water-Soluble Imidazolium Polyesters as Potential Nonviral Gene Delivery Vehicles. Biomacromolecules 2017, 18 (1), 68–76. https://doi.org/10.1021/acs.biomac.6b01316.
(44) Miyata, K.; Oba, M.; Nakanishi, M.; Fukushima, S.; Yamasaki, Y.; Koyama, H.; Nishiyama, N.; Kataoka, K. Polyplexes from Poly(Aspartamide) Bearing 1,2-Diaminoethane Side Chains Induce PH-Selective, Endosomal Membrane Destabilization with Amplified Transfection and Negligible Cytotoxicity. J. Am. Chem. Soc. 2008, 130 (48), 16287–16294. https://doi.org/10.1021/ja804561g.
(45) Sprouse, D.; Reineke, T. M. Investigating the Effects of Block versus Statistical Glycopolycations Containing Primary and Tertiary Amines for Plasmid DNA Delivery. Biomacromolecules 2014, 15 (7), 2616–2628. https://doi.org/10.1021/bm5004527.
(46) Dalal, R. J.; Kumar, R.; Ohnsorg, M.; Brown, M.; Reineke, T. M. Cationic Bottlebrush Polymers Outperform Linear Polycation Analogues for PDNA Delivery and Gene Expression. ACS Macro Lett. 2021, 10 (7), 886–893. https://doi.org/10.1021/acsmacrolett.1c00335.
(47) McLendon, P. M.; Fichter, K. M.; Reineke, T. M. Poly(Glycoamidoamine) Vehicles Promote PDNA Uptake through Multiple Routes and Efficient Gene Expression via Caveolae-Mediated Endocytosis. Mol. Pharm. 2010, 7 (3), 738–750. https://doi.org/10.1021/mp900282e.
(48) Certo, M. T.; Ryu, B. Y.; Annis, J. E.; Garibov, M.; Jarjour, J.; Rawlings, D. J.; Scharenberg, A. M. Tracking Genome Engineering Outcome at Individual DNA Breakpoints. Nat. Methods 2011, 8 (8), 671–676. https://doi.org/10.1038/nmeth.1648.
(49) Sayres, R.; Taly, A.; Rahimy, E.; Blumer, K.; Coz, D.; Hammel, N.; Krause, J.; Narayanaswamy, A.; Rastegar, Z.; Wu, D.; Xu, S.; Barb, S.; Joseph, A.; Shumski, M.; Smith, J.; Sood, A. B.; Corrado, G. S.; Peng, L.; Webster, D. R. A Unified Approach to Interpreting Model Predictions. Proc. 31st Int. Conf. Neural Inf. Process. Syst. 2017, pp 4768−4777. https://doi.org/10.1016/j.ophtha.2018.11.016.
(50) Tan, Z.; Jiang, Y.; Ganewatta, M. S.; Kumar, R.; Keith, A.; Twaroski, K.; Pengo, T.; Tolar, J.; Lodge, T. P.; Reineke, T. M. Block Polymer Micelles Enable CRISPR/Cas9 Ribonucleoprotein Delivery: Physicochemical Properties Affect Packaging Mechanisms and Gene Editing Efficiency. Macromolecules 2019, 52 (21), 8197–8206. https://doi.org/10.1021/acs.macromol.9b01645.
(51) Tolstyka, Z. P.; Phillips, H.; Cortez, M.; Wu, Y.; Ingle, N.; Bell, J. B.; Hackett, P. B.; Reineke, T. M. Trehalose-Based Block Copolycations Promote Polyplex Stabilization for Lyophilization and in Vivo PDNA Delivery. ACS Biomater. Sci. Eng. 2016, 2 (1), 43–55. https://doi.org/10.1021/acsbiomaterials.5b00312.
(52) Podetz-Pedersen, K. M.; Bell, J. B.; Steele, T. W. J.; Wilber, A.; Shier, W. T.; Belur, L. R.; McIvor, R. S.; Hackett, P. B. Gene Expression in Lung and Liver After Intravenous Infusion of Polyethylenimine Complexes of Sleeping Beauty Transposons. Hum. Gene Ther. 2010, 21 (2), 210–220. https://doi.org/10.1089/hum.2009.128.
(53) Bell, J. B.; Podetz-Pedersen, K. M.; Aronovich, E. L.; Belur, L. R.; McIvor, R. S.; Hackett, P. B. Preferential Delivery of the Sleeping Beauty Transposon System to Livers of Mice by Hydrodynamic Injection. Nat. Protoc. 2007, 2 (12), 3153–3165. https://doi.org/10.1038/nprot.2007.471.