Gene therapy shows great promise to treat both acquired and inherited diseases.Numerous gene delivery systems based on viral and nonviral vectors have been developed to protect plasmid DNA and facilitate cell binding and internalization.Nevertheless

it is still a challenge to deliver DNA to target cell population and particular location by injection or systematic delivery due to the immune responses and DNA complex aggregation

degradation

and clearance from the tissue.Polymers loaded with gene or vector/gene complexes can realize the controlled release of gene delivery systems and direct gene delivery to target tissues.This technique

known as “substratemediated transfection"

overcomes the extracelluar barriers of gene delivery

sustains the gene release

decreases the toxicity and consequently improves the gene transfection efficiency.Most commonly

the polymers for the controlled release of gene delivery systems are biodegradable polymers.Using these polymers

a variety of formulations of controlled release systems

including nanoparticles

microspheres

implantable matrices and scaffolds

can be fabricated.This review focuses on the recent developments in the polymers used for the controlled release of gene delivery systems

with emphasis on their applications in gene therapy and tissue engineering.These polymers are classified as natural polymers and their derivatives such as collagen

atelocollagen

gelatin

fibrin

glycosaminoglycans

chitosan

alginate

and agarose

and synthetic polymers including poly(lactide-co-glycolide)

poly(lactic acid)

functionalized poly(lactic acid)

poly(orthoester)s

poly( β-amino ester)s

polyanhydrides

polyurethanes and poly(ethylene-co-vinylacetate).Looking to the future

through exquisite adjusting of the chemical and physical characteristics of the polymers

optimally engineered properties may be created to gain greater control over gene expression and cell growth.