Cleft palates. Grievous wounds. Lost hands or faces. All could be repaired more completely than is currently possible if genetic editing were to become an integral part of plastic and reconstructive surgery. This possibility is receiving serious consideration now that CRISPR gene editing, a powerful research tool, is being developed for clinical applications. CRISPR could also enhance cosmetic interventions, by modifying genetic targets implicated in hair loss and the aging of skin. Also, the humanization of donor animals with CRISPR could result in the production of novel fillers that are less immunogenic and less costly.
These potential applications, however, will be realized only if professionals in plastic and reconstructive surgery become “stakeholders in CRISPR gene editing and participate in future debates on the ethical use of CRISPR for the betterment of our patients,” write the authors of an article appearing in the November issue of Plastic and Reconstructive Surgery. This article, “CRISPR Craft: DNA Editing the Reconstructive Ladder,” is the work of surgeons and clinical scientists based at Massachusetts General Hospital and Harvard Medical School.
“CRISPR’s potential impact on treating human disease includes several areas important to the plastic surgeon such as oncology, wound healing, immunology, and craniofacial malformations,” comments the article’s senior author, Eric Chien-Wei Liao, M.D., Ph.D., associate professor of surgery, Harvard Medical School. Dr. Liao is also director, Cleft and Craniofacial Center, and principal investigator, Center for Regenerative Medicine, Harvard Stem Cell Institute.
In their article, Dr. Liao and colleagues discuss some key areas where CRISPR has foreseeable implications for plastic surgery, including:
- Craniofacial Malformations. Basic science studies using CRISPR techniques have already led to new insights into craniofacial developmental pathways. CRISPR enables quick identification of individual gene mutations, and may one day lead to the ability to correct mutations and prevent the development of cleft lip, cleft palate, and other congenital malformations.
- Wound Healing and Tissue Repair. Gene therapy is a promising approach to enhancing wound and tissue healing. In addition to accelerated healing of skin wounds, CRISPR may lead to new approaches for repair and regeneration of bone, cartilage, nerve, and muscle.
- Cell Therapy and Tissue Engineering. Genetic techniques may enable the creation or modification of the patient’s own (autologous) cells to graft or replace damaged tissues, stimulate cell development, or modulate immune functions. “[Techniques] of creating skin grafts with therapeutic potential would have widespread impact in reconstructive surgery,” Dr. Liao and coauthors write.
- Flap Biology and Transplants. In addition to modifying tissue flaps, gene editing with CRISPR may make it possible to reprogram vascularized composite allotransplants—such as face or hand transplants—to promote tolerance and prevent rejection by the recipient’s immune system. Similar immune modulation approaches might also promote tolerance of tissues from animal donors (xenotransplantation).
“CRISPR is a major technological advance revolutionizing broad areas of oncology, wound healing, immunology, and craniofacial genetics, such that plastic surgeons should gain familiarity with this disruptive technology, and become active contributors and leaders in applying CRISPR to our respective areas of expertise,” the authors of the current article maintain. “New rungs of the reconstructive ladder may one day be modified to include molecular enhancement of tissue repair with CRISPR gene editing, administration of CRISPR-edited cells with enhanced survival, or even transplantation of humanized tissues from CRISPR-edited animals.”
Dr. Liao and colleagues emphasized that many challenges remain in realizing these and other clinical advances with CRISPR gene editing, including potential “off-target” effects, FDA regulation, high costs, and ethical issues related to genetic editing of human cells and tissues.