A treatment method and genetic vectors are disclosed for non-invasive deliveryof polypeptides through the blood brain barrier (BBB), to treat brain orspinal tissue. A genetic vector is used to transfect one or more neurons which"straddle" the BBB, such as sensory neurons, nocioceptive neurons, or lowermotor neurons； this is done by administering the vector in a manner thatcauses it to contact neuronal projections that extend outside the BBB. Onceinside a peripheral projection that belongs to a BBB-straddling neuron, thevectors (or some portion thereof) will be transported to the main cell body ofthe neuron, through a process called retrograde transport. Inside the maincell body, at least one gene carried by the genetic vector will be expressed,to form polypeptides. Some of these polypeptides (which can include leadersequences that will promote anterograde transport and secretion by BBB-straddling neurons) will be transported by the neurons to secretion sitesinside the BBB. The polypeptides will be secreted by transfected neurons atlocations inside the BBB, and will then contact and exert their effects uponsecondary "target" neurons located entirely within the BBB. By using thissystem, polypeptides that stimulate nerve growth or activity can be used totreat neurodegenerative diseases, impaired limbs in stroke victims, etc., andpolypeptides that suppress neuronal activity can be used to treat unwantedexcessive neuronal activity, such as neuropathic pain. This approach alsoprovides new methods for delivering endocrine and paracrine polypeptides intothe CNS, thereby allowing improved medical and reproductive treatments inhumans, and improved ability to modulate growth, maturation, reproduction, orother endocrine-related functions among livestock, endangered species, andother animals.
