Integration of drug, protein, and gene delivery systems with regenerative medicine - PubMed (original) (raw)

Review

Integration of drug, protein, and gene delivery systems with regenerative medicine

Elizabeth R Lorden et al. Drug Deliv Transl Res. 2015 Apr.

Abstract

Regenerative medicine has the potential to drastically change the field of health care from reactive to preventative and restorative. Exciting advances in stem cell biology and cellular reprogramming have fueled the progress of this field. Biochemical cues in the form of small molecule drugs, growth factors, zinc finger protein transcription factors and nucleases, transcription activator-like effector nucleases, monoclonal antibodies, plasmid DNA, aptamers, or RNA interference agents can play an important role to influence stem cell differentiation and the outcome of tissue regeneration. Many of these biochemical factors are fragile and must act intracellularly at the molecular level. They require an effective delivery system, which can take the form of a scaffold (e.g., hydrogels and electrospun fibers), carrier (viral and nonviral), nano- and microparticle, or genetically modified cell. In this review, we will discuss the history and current technologies of drug, protein, and gene delivery in the context of regenerative medicine. Next, we will present case examples of how delivery technologies are being applied to promote angiogenesis in nonhealing wounds or prevent angiogenesis in age related macular degeneration. Finally, we will conclude with a brief discussion of the regulatory pathway from bench to bedside for the clinical translation of these novel therapeutics.

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Conflict of interest statement

Conflict of Interest

Elizabeth Lorden, Howard Levinson, and Kam Leong all declare they have no conflict of interest.

Figures

Fig. 1

Fig. 1

Parallel advancements in the use of drugs, proteins, and genes for regenerative therapeutics converged in the 1990’s with the need for rationally designed delivery systems

Fig. 2

Fig. 2

Visualization of protein-based cues. Growth factors interact with cells via transmembrane receptors to drive various processes such as differentiation, migration or proliferation (A). Each zinc finger protein recognizes 3–4 base pairs, such that a modular construct of multiple ZFPs can be generated to recognize a unique sequence in the genome (B). Monoclonal antibodies recognize specific antigens within the body, once bound to their target they can either physically inactivate it or recruit immune cells to destroy it (C)

Fig. 3

Fig. 3

Delivery vehicles for small molecule drugs, proteins, and nucleic acids. Carriers for soluble factors can be macroscopic, such as hydrogels (A) and electrospun fibers (B), or microscopic, such as micelles and liposomes (C.1), dendrimers (C.2), or particulate hydrogel systems (C.3). Carriers for nucleic acids such as DNA, RNA and plasmid DNA have unique design requirements since they must be able to carry their negatively charged cargo across the negatively charged cellular membrane. Viral carriers (D) can be used to introduce DNA into cells, most commonly done in vitro to generate genetically modified cells (E). Non-viral delivery methods can include simple complexation with cationic polymers (F.1), or the use of particulate systems such as liposomes (F.2) and lipopolyplexes (F.3). These methods can also be used to generate genetically modified cells or deliver nucleic acid cargo in vivo

Fig. 4

Fig. 4

Carrier Selection Guide. Selection of the correct delivery vehicle must first consider whether the soluble factor is active intracellularly or if extracellular delivery is optimal. Once delivery method is chosen, the delivery method of the carrier should be selected based on disease pathogenesis. Injection of microscopic carriers may be optimal for systemic or localized pathogenesis, while implantation of 3D scaffold carriers are most effective when repairing a tissue defect

Fig. 5

Fig. 5

Technology Patent Protection and the steps to clinical translation

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References

    1. Hasetine W. A brave new medicine. A conversation with William Haseltine. Interview by Joe Flower. Health Forum journal. 1999;42(4):28–30. 61–65. - PubMed
    1. Chen FM, Zhao YM, Jin Y, Shi S. Prospects for translational regenerative medicine. Biotechnology advances. 2012;30(3):658–672. - PubMed
    1. Couto DS, Perez-Breva L, Cooney CL. Regenerative medicine: learning from past examples. Tissue engineering Part A. 2012;18(21–22):2386–2393. - PubMed
    1. Takahashi K, Yamanaka S. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell. 2006;126(4):663–676. doi: http://dx.doi.org/10.1016/j.cell.2006.07.024. - DOI - PubMed
    1. Davis RLWH, Lassar AB. Expression of a single transfected cDNA converts fibroblasts to myoblasts. Cell. 1987;51(6):987–1000. - PubMed

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