A virus that has had its genetic material re-

moved has been used for the first time as a

molecular container. The US researchers behind

this work have used the virus for carrying drugs

and other small molecules, and this discovery

presents an opportunity to attempt to tailor the

viral coat – virion – to provide a highly targeted

and very specific drug delivery system. This new

system could enable a smaller dose to be given

to the patient and also reduce the side-effects

that are caused by peripheral damage to

healthy tissue.

The idea of using viruses as medical agents is

not new. Vaccines are the classic example of

eliciting a useful medical response with a virus,

and the use of viruses as carriers, or vectors, for

gene therapy is currently being investigated in

earnest. Until now, the use of a virus to contain

a distinct chemical species, such as a drug, has

not been attempted but chemist Trevor Douglas

(Temple University, Philadelphia, PA, USA) and

plant pathologist Mark Young (Montana State

University, Bozeman, MT, USA) have recently

used a simple plant virus as a nanoscale drug

capsule1.

Douglas and Young used what they term a

pH-dependent ‘gating mechanism’ of the virion

(Fig. 1). This takes the viral coat through a re-

versible structural transition, a swelling, which

results in holes in the virion opening up and

through which viral nucleic acids can be re-

moved and a new payload inserted. Douglas

explains that, ‘In their native state, viruses are

protein assemblies, which act as host containers

for nucleic acid storage and transport. We have

subverted this natural function’. He adds, ‘The

swelling of the virion has been known for a

long time ... we have used it as a way of re-

versibly encapsulating non-genetic materials’.

To demonstrate the technique, the re-

searchers used a polyanetholesulphonic acid

analogue of heparin – routinely used in treating

coronary thrombosis – and inserted it success-

fully into the empty husk of a cowpea chlorotic

mottle virus. The gating phenomenon is, they

say, available to be exploited in a large number

of viruses, so there is no reason why drug

delivery would be limited to any particular class

of pharmaceuticals. ‘Even [in] the smallest

”container“, we are loading many (tens, hun-

dreds or thousands) of copies of any mol-

ecule/drug,' adds Douglas.

Not only has the team subverted successfully a

virus function, but they can also go routinely (but

not easily, admits Douglas) one step further and

modify the design of the virion outer surface. This

means that the loaded virus can be altered to tar-

get certain types of cells (such as cancer cells) and

holds the promise of highly targeted drug deliv-

ery. According to Young, there should not be a

problem with safety issues as the viruses that he

and Douglas have hitherto worked with are rela-

tively simple plant viruses. These viruses are in-

credibly host-specific to the plant. Indeed, we eat

related viruses inadvertently – with the exception

of that from cowpea, Douglas jokes – with no ill

effects every day in fruit and vegetables. The viral

containers are gene-free and so they are inactive

as infectious agents.

Chemists have had varying degrees of suc-

cess in the past few years in making container

molecules from scratch. The fact that container

molecules can be adapted in this way could

open up new avenues of design, allowing the

chemist to apply their skills to modifying natu-

ral ingredients for drug delivery without the

need to build from first principles.

Reference01 Douglas,T. and Young, M. (1998) Nature 393,

152

update news PSTT Vol. 1, No. 4 July 1998

146

Smuggling drugs in a viral coatDavid Bradley, tel/fax: +44 1954 202218, Web: http://www.camsoft.com/elemental/

Copyright ©1998 Elsevier Science Ltd. All rights reserved. 1461-5347/98/$19.00.

Figure 1. Images reconstructed fromcryoelectron microscopy of cowpea chloroticmottle virus at low (left) and high (right) pHshow openings in the viral shell when the pHis raised. Images courtesy of Timothy S. Baker,Purdue University and Nature.

There are approximately 1 million Parkinson’s dis-

ease (PD) patients in Europe, and more than

100,000 new cases are diagnosed each year.

Against a setting of increasing incidence of young-

onset cases and an aging population, it is clear that

the prevalence of this disease is on the increase.

Burden of symptomsA common problem with existing PD therapies

is that, after continued use, the efficacy gradu-

ally declines and drug-induced side effects,

such as dyskinesia, often worsen as higher

doses are required.

A surgically implanted device, Activa™

therapy (Medtronic, Minneapolis, MN, USA),

may alleviate the associated healthcare burden

by giving many PD patients their independence

back. The device delivers mild electrical stimu-

lation to block the brain signals that cause the

Device offers better control in Parkinson’s diseaseSimon Fenwick, Pharmaceutical Science & Technology Today, tel: 144 1223 315961, fax: 144 1223 464430, e-mail: pstt@elsevier.co.uk