The Evolving Landscape of Gene Therapy in Plastic Surgery

Abstract

With the rapid rise of personalized genomic sequencing and clustered regularly interspaced short palindromic repeat (CRISPR) technology, previous gaps in gene therapy are beginning to be bridged, paving the way for increasing clinical applicability. This article aims to provide an overview of the fundamentals of gene therapy and discuss future potential interventions relevant to plastic surgeons. These interventions include enhancing tissue regeneration and healing, as well as modifying disease processes in congenital anomalies. Though clinical applications are still on the horizon, a deeper understanding of these new advances will help plastic surgeons understand the current landscape of gene therapy and stay abreast of future opportunities.

Keywords

gene therapy - gene delivery - CRISPR - plastic surgery

• References

• 1 Lyerly HK. Gene therapy in surgery. Ann Surg 1996; 223 (02) 115
• 2 Tepper OM, Mehrara BJ. Gene therapy in plastic surgery. Plast Reconstr Surg 2002; 109 (02) 716-734
• 3 Ghali S, Dempsey MP, Jones DM, Grogan RH, Butler PE, Gurtner GC. Plastic surgical delivery systems for targeted gene therapy. Ann Plast Surg 2008; 60 (03) 323-332
• 4 Bett AJ, Prevec L, Graham FL. Packaging capacity and stability of human adenovirus type 5 vectors. J Virol 1993; 67 (10) 5911-5921
• 5 Evans CH, Ghivizzani SC, Oligino TA, Robbins PD. Future of adenoviruses in the gene therapy of arthritis. Arthritis Res 2001; 3 (03) 142-146
• 6 Powell SK, Kaloss M, Burimski I. , et al. In vitro analysis of transformation potential associated with retroviral vector insertions. Hum Gene Ther 1999; 10 (13) 2123-2132
• 7 Purcell DF, Broscius CM, Vanin EF, Buckler CE, Nienhuis AW, Martin MA. An array of murine leukemia virus-related elements is transmitted and expressed in a primate recipient of retroviral gene transfer. J Virol 1996; 70 (02) 887-897
• 8 Muzyczka N. Use of adeno-associated virus as a general transduction vector for mammalian cells. Curr Top Microbiol Immunol 1992; 158: 97-129
• 9 Miao CH, Nakai H, Thompson AR. , et al. Nonrandom transduction of recombinant adeno-associated virus vectors in mouse hepatocytes in vivo: cell cycling does not influence hepatocyte transduction. J Virol 2000; 74 (08) 3793-3803
• 10 Varghese S, Rabkin SD. Oncolytic herpes simplex virus vectors for cancer virotherapy. Cancer Gene Ther 2002; 9 (12) 967-978
• 11 Kircheis R, Wightman L, Schreiber A. , et al. Polyethylenimine/DNA complexes shielded by transferrin target gene expression to tumors after systemic application. Gene Ther 2001; 8 (01) 28-40
• 12 Yamashita Y, Shimada M, Tachibana K. , et al. In vivo gene transfer into muscle via electro-sonoporation. Hum Gene Ther 2002; 13 (17) 2079-2084
• 13 Globus RK, Patterson-Buckendahl P, Gospodarowicz D. Regulation of bovine bone cell proliferation by fibroblast growth factor and transforming growth factor beta. Endocrinology 1988; 123 (01) 98-105
• 14 Sampath TK, Reddi AH. Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. Proc Natl Acad Sci U S A 1981; 78 (12) 7599-7603
• 15 Spector JA, Mehrara BJ, Luchs JS. , et al. Expression of adenovirally delivered gene products in healing osseous tissues. Ann Plast Surg 2000; 44 (05) 522-528
• 16 Scaduto AA, Lieberman JR. Gene therapy for osteoinduction. Orthop Clin North Am 1999; 30 (04) 625-633
• 17 Franceschi RT, Wang D, Krebsbach PH, Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem 2000; 78 (03) 476-486
• 18 Musgrave DS, Bosch P, Ghivizzani S, Robbins PD, Evans CH, Huard J. Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone 1999; 24 (06) 541-547
• 19 Breitbart AS, Mason JM, Urmacher C. , et al. Gene-enhanced tissue engineering: applications for wound healing using cultured dermal fibroblasts transduced retrovirally with the PDGF-B gene. Ann Plast Surg 1999; 43 (06) 632-639
• 20 Fang J, Zhu YY, Smiley E. , et al. Stimulation of new bone formation by direct transfer of osteogenic plasmid genes. Proc Natl Acad Sci U S A 1996; 93 (12) 5753-5758
• 21 Haase G, Kennel P, Pettmann B. , et al. Gene therapy of murine motor neuron disease using adenoviral vectors for neurotrophic factors. Nat Med 1997; 3 (04) 429-436
• 22 Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999; 341 (10) 738-746
• 23 Lawrence WT, Diegelmann RF. Growth factors in wound healing. Clin Dermatol 1994; 12 (01) 157-169
• 24 Crombleholme TM. Adenoviral-mediated gene transfer in wound healing. Wound Repair Regen 2000; 8 (06) 460-472
• 25 Strickland JW. Management of acute flexor tendon injuries. Orthop Clin North Am 1983; 14 (04) 827-849
• 26 Lou J, Tu Y, Burns M, Silva MJ, Manske P. BMP-12 gene transfer augmentation of lacerated tendon repair. J Orthop Res 2001; 19 (06) 1199-1202
• 27 Greenwald JA, Mehrara BJ, Spector JA. , et al. In vivo modulation of FGF biological activity alters cranial suture fate. Am J Pathol 2001; 158 (02) 441-452
• 28 Wang E, Nam HK, Liu J, Hatch NE. The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis. Orthod Craniofac Res 2015; 18 (Suppl. 01) 196-206
• 29 Johnson KA, Hessle L, Vaingankar S. , et al. Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC-1. Am J Physiol Regul Integr Comp Physiol 2000; 279 (04) R1365-R1377
• 30 Hessle L, Johnson KA, Anderson HC. , et al. Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization. Proc Natl Acad Sci U S A 2002; 99 (14) 9445-9449
• 31 Twigg SR, Healy C, Babbs C. , et al. Skeletal analysis of the Fgfr3(P244R) mouse, a genetic model for the Muenke craniosynostosis syndrome. Dev Dyn 2009; 238 (02) 331-342
• 32 Thomas SM, Grandis JR. The current state of head and neck cancer gene therapy. Hum Gene Ther 2009; 20 (12) 1565-1575
• 33 Farmer ZL, Kim ES, Carrizosa DR. Gene therapy in head and neck cancer. Oral Maxillofac Surg Clin North Am 2019; 31 (01) 117-124
• 34 Zaoui K, Bossow S, Grossardt C. , et al. Chemovirotherapy for head and neck squamous cell carcinoma with EGFR-targeted and CD/UPRT-armed oncolytic measles virus. Cancer Gene Ther 2012; 19 (03) 181-191
• 35 Moon C, Oh Y, Roth JA. Current status of gene therapy for lung cancer and head and neck cancer. Clin Cancer Res 2003; 9 (14) 5055-5067
• 36 Shimada H, Matsubara H, Shiratori T. , et al. Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma. Cancer Sci 2006; 97 (06) 554-561
• 37 Birkeland AC, Ludwig ML, Spector ME, Brenner JC. The potential for tumor suppressor gene therapy in head and neck cancer. Discov Med 2016; 21 (113) 41-47
• 38 Kennedy EM, Kornepati AV, Goldstein M. , et al. Inactivation of the human papillomavirus E6 or E7 gene in cervical carcinoma cells by using a bacterial CRISPR/Cas RNA-guided endonuclease. J Virol 2014; 88 (20) 11965-11972
• 39 Rezende FC, Gomes HC, Lisboa B, Lucca AF, Han SW, Ferreira LM. Electroporation of vascular endothelial growth factor gene in a unipedicle transverse rectus abdominis myocutaneous flap reduces necrosis. Ann Plast Surg 2010; 64 (02) 242-246
• 40 Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997; 18 (01) 4-25
• 41 Mir LM, Moller PH, André F, Gehl J. Electric pulse-mediated gene delivery to various animal tissues. Adv Genet 2005; 54: 83-114
• 42 Sambrook J, Gething MJ. Protein structure. Chaperones, paperones. Nature 1989; 342 (6247): 224-225
• 43 Michaels V J, Dobryansky M, Galiano RD. , et al. Ex vivo transduction of microvascular free flaps for localized peptide delivery. Ann Plast Surg 2004; 52 (06) 581-584
• 44 Ghali S, Bhatt KA, Dempsey MP. , et al. Treating chronic wound infections with genetically modified free flaps. Plast Reconstr Surg 2009; 123 (04) 1157-1168
• 45 Carruthers KH, During MJ, Muravlev A, Wang C, Kocak E. Fat grafting as a vehicle for the delivery of recombinant adenoassociated viral vectors to achieve gene modification of muscle flaps. Ann Plast Surg 2013; 70 (06) 726-731
• 46 Roh DS, Li EB, Liao EC. CRISPR craft: DNA editing the reconstructive ladder. Plast Reconstr Surg 2018; 142 (05) 1355-1364
• 47 Roman S, Lindeman R, O'Toole G, Poole MD. Gene therapy in plastic and reconstructive surgery. Curr Gene Ther 2005; 5 (01) 81-99
• 48 Nelson CE, Hakim CH, Ousterout DG. , et al. In vivo genome editing improves muscle function in a mouse model of Duchenne muscular dystrophy. Science 2016; 351 (6271): 403-407
• 49 Jubbal KT, Zavlin D, Suliman A. The effect of age on microsurgical free flap outcomes: an analysis of 5,951 cases. Microsurgery 2017; 37 (08) 858-864
• 50 Kosaric N, Srifa W, Gurtner G, Porteus M. Abstract 100: human mesenchymal stromal cells engineered to overexpress PDGF-B using CRISPR/Case9/rAAV6-based tools to improve wound healing. Plast Reconstr Surg Glob Open 2017; 5 (Suppl. 04) 74
• 51 Eming SA, Krieg T, Davidson JM. Gene therapy and wound healing. Clin Dermatol 2007; 25 (01) 79-92
• 52 Brennan TA, Wilson JM. The special case of gene therapy pricing. Nat Biotechnol 2014; 32 (09) 874-876
• 53 Schultz B, Yao X, Deng Y. , et al. A common polymorphism within the IGF2 imprinting control region is associated with parent of origin specific effects in infantile hemangiomas. PLoS One 2015; 10 (10) e0113168