Table 1.
Delivery systems under development
| Delivery system | Target tissue | Administration | Cargo classa | PI(s)b |
|---|---|---|---|---|
| Viral: AAV | Brain | Intravenous | DNA | B. E. Deverman |
| Viral: AAV | Endothelium | Intravenous | DNA | G. Bao, W. R. Lagor |
| Viral: adenovirus | Endothelium | Intravenous | DNA | D. T. Curiel |
| Viral: AAV | Brain, skeletal muscle | Intravenous | DNA | A. Asokan, C. Gersbach |
| Non-viral: engineered guide RNAs | Brain | Local injection | RNP | E. J. Sontheimer, A. Khvorova, J. K. Watts, S. A. Wolfe |
| Non-viral: polymeric NP | Bone marrow, lung | Intravenous | mRNA, PNA | W. M. Saltzman, P. M. Glazer |
| Non-viral: polymeric NP | Brain | Local injection, intravenous | RNP | S. Gong, M. Emborg, J. E. Levine, S. Roy, K. Saha |
| Non-viral: polymeric NP | Brain | CED, intravenous | RNP | J. Zhou |
| Non-viral: cell-targeted NP | HSPCs | Intravenous | mRNA | J. Dahlman, P. J. Santangelo |
| Non-viral: liposomal NP | Inner ear | Local injection | mRNA, RNP | Z. Chen, D. R. Liu, Q. Xu |
| Non-viral: extracellular vesicles | Bone marrow | Intravenous | mRNA, RNP | I. Ghiran |
| Non-viral: PEGylated particles | Brain | CED | RNP | K. S. Bankiewicz, N. Murthy |
| Non-viral: ultrasound | Brain | Intravenous | DNA, RNP | K. W. Leong |
| Non-viral: amphiphilic peptides | Lung epithelium | Nasal instillation | RNP | P. McCray |
| Non-viral: engineered RNP | Immune cells | Intravenous | RNP | R. Wilson, J. A. Doudna |
| Non-viral: engineered RNP, VLP | HSPCs | Intravenous | RNP | E. Chaikof |
| Non-viral: engineered capsids | Intestinal cell types | Oral, intravenous | DNA, mRNA, RNP | K. Lam, R. H. Cheng |
| Non-viral: VLP | T cells | Intravenous | RNP | G. Yi |
| Non-viral: VLP | Lung, gastrointestinal tract | Intravenous | RNP | J. C. Tilton, M. Drumm, C. Flask, Z. Wang |
| Hybrid: NP and AAV | Lung epithelium | Inhalation/intratracheal | DNA, mRNA | G. Gao, D. G. Anderson, W. Xue |
CED, convection-enhanced delivery; HSPCs, haematopoietic stem and progenitor cells; NP, nanoparticle; VLP, virus-like particle.
a‘Cargo’ refers to the molecular form(s) of genome-editing enzyme component(s): DNA encoding protein and guide RNA, mRNA encoding protein co-delivered with guide RNA, a RNP complex or a PNA.
bThe lead principal investigator (PI) of the project is listed first. Additional PIs follow, listed alphabetically by last name.