Table 3.

Characteristics, advantages, and limitations of commonly investigated vectors used in corneal gene therapy.

Vectors Properties	Adenovirus	Retrovirus	Lentivirus	HSV	AAV	Nanoparticle	Non-viral
Virus family	Adenoviridae	Retrovirdae	Retrovirdae	Herpesviridae	Parvoviridae	–	–
Size of vector	70–90 nm	80–130 nm	80–130 nm	120–300 nm	18–26 nm	1–100 nm	≥500 nm
Size of genome	38–39 kb	3–9 kb	3–9 kb	152 kb	4.7 kb	–	–
Type	dsDNA	ssRNA	ssRNA	dsDNA	ssDNA	Chemicals	Chemicals
Size of virion	70–90 nm	80–130 nm	80–130 nm	120–300 nm	18–26 nm	–	–
Integration in host genome	No	Yes	No, Yes (if impaired)	No	No	No	No
Transduction efficiency	Low - High	Moderate - High	High	Low - High	Moderate - High	Moderate - High	Low - Moderate
Delivered-gene time duration	Days - Weeks	Months -Years	Months -Years	Days - Weeks	Weeks -Months	Hours -Months	Hours - Days
Immunogenicity	High	Moderate -High	Moderate -High	Low - Moderate	Low -Moderate	Low - High	Low
Ability to deliver genes into cells	Dividing	Dividing	Dividing and Non-dividing	Dividing	Dividing and Non-dividing	Dividing and Non-dividing	Dividing and Non-dividing
Therapeutic load carrying capacity	≤7.5 kb	≤8 kb	≤8 kb	≤30 kb	≤1.8 kb	No limit	No limit
Advantages	Highly efficacious for proliferating corneal cells in vivo, in vitro and ex vivo, easily available, high success rate, non-mutagenic	Highly efficient for gene delivery into all major corneal cells in vivo, and ex vivo, provide high and long-term delivered-gene expression, high success rate, low immune reaction in host	High efficiency for delivering genes into all 3 major corneal cells and stem cells, sustained delivered-gene expression, new generation LVs are efficacious and safe, widely useful for in vitro gene therapy concept testing and expression profiling	Good for delivering genes in most of corneal cells, long-term high levels in vivo transgene expression	Highly efficient for delivering genes in dividing and non-dividing corneal cells in vivo, in vitro, and ex vivo, stable transgene expression, high and extended-time delivered-gene expression, low/no immune reaction, many serotypes, low safety risk, site-specific integration	Highly potent and safe for corneal cells, low immune reaction, multi-encapsulation ability, any size therapeutic gene transportation capacity, allows tracking while in cell/tissue, ability to dictate release of therapeutics	Mostly harmless and safe, induce mild local immune reaction, deliver large therapeutic genes, cost effective, easy commercial production
Limitations	High immune reaction, repeat doses ineffective, high safety risk, can harm caregiver, short-term gene expression	Variable in vivo gene transfer due to dependence on target cell mitosis, requires dividing cells, low titer, safety concerns, random integration	HIV origin, high immunogenicity, safety concerns, titer production pleads technical skills	Difficult to produce in large quantities	Small insert size, production needs technical skills, concerns of AV contamination	Not all NP show same response, often optimization required, variable gene transfer efficiency, short-term transgene expression	Poor efficiency, low-high immune reaction, short-term transgene expression