Retargeting of adenoviral gene delivery via Herceptin–PEG–adenovirus conjugates to breast cancer cells

Jung, Yukyung; Park, Hyojin; Kim, Pyung Hwan; Lee, Jaewon; Hyung, Woochan; Yang, Jaemoon; Ko, Hyun-Ju; Sohn, Joohyuk; Kim, Joo Hang; Huh, Yong Min; Yun, Chae Ok; Haam, Seungjoo

doi:10.1016/j.jconrel.2007.08.002

Cited by 49 publications

(35 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Masking of molecular patterns on the Ad capsid by PEGylation was previously evidenced by a significant reduction in innate immune responses. After 6 hr of intravenous administration of PEGylated Ad, the plasma level of IL-6, which is the main indicator of an innate immune response against Ad, was reduced by 95% compared to that of naked Ad (22).…”

Section: Polymer Complexes With Polyethylene Glycol (Peg) and Poly-n-mentioning

confidence: 98%

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

Kang

Yun

2010

BMB Reports

Self Cite

View full text Add to dashboard Cite

Section: Polymer Complexes With Polyethylene Glycol (Peg) and Poly-n-mentioning

confidence: 98%

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

Kang

Yun

2010

BMB Reports

Self Cite

View full text Add to dashboard Cite

“…As a result of the broad distribution of the coxsackie-adenovirus receptor (CAR) and significant interactions with alternative receptors, most gene delivery applications benefit from more restrictive vector targeting. As a result, significant effort is being invested in both transductional and transcriptional targeting of these vectors (1,2,13). Transductional targeting efforts take advantage of three different methods for capsid remodeling: genetic, noncovalent, and chemical modification.…”

mentioning

confidence: 99%

“…Lysine modification allows a high degree of functionalization with immunosuppressive polymers, targeting polypeptides and imaging reagents. Conjugation of polyethylene glycol (PEG) polymers allows production of "stealth" vectors, which are both protected from immune recognition and effectively detargeted (13,17,25). Further, PEG polymers can be armed with targeting moieties, allowing the vector to be efficiently retargeted in a single step.…”

mentioning

confidence: 99%

Unnatural Amino Acid Incorporation onto Adenoviral (Ad) Coat Proteins Facilitates Chemoselective Modification and Retargeting of Ad Type 5 Vectors

Banerjee

Ostapchuk

Hearing

et al. 2011

J Virol

View full text Add to dashboard Cite

Surface modification of adenovirus vectors can improve tissue-selective targeting, attenuate immunogenicity, and enable imaging of particle biodistribution, thus significantly improving therapeutic potential. Currently, surface engineering is constrained by a combination of factors, including impact on viral fitness, limited access to functionality, or incomplete control over the site of modification. Here, we report a two-step labeling process involving an initial metabolic placement of a uniquely reactive unnatural amino acid, azidohomoalanine (Aha), followed by highly specific chemical modification. As genetic modification of adenovirus is unnecessary, vector production is exceedingly straightforward. Aha incorporation demonstrated no discernible impact on either virus production or infectivity of the resultant particles. "Click" chemical modification of surface-exposed azides was highly selective, allowing for the attachment of a wide range of functionality. Decoration of human adenovirus type 5 (hAd5) with folate, a known cancer-targeting moiety, provided an ϳ20-fold increase in infection of murine breast cancer cells (4T1) in a folate receptor-dependent manner. This study demonstrates that incorporation of unnatural amino acids can provide a flexible, straightforward route for the selective chemical modification of adenoviral vectors.Adenoviruses (Ad) are widely employed vehicles for gene replacement, cancer gene delivery, and vaccine development. As a result of the broad distribution of the coxsackie-adenovirus receptor (CAR) and significant interactions with alternative receptors, most gene delivery applications benefit from more restrictive vector targeting. As a result, significant effort is being invested in both transductional and transcriptional targeting of these vectors (1, 2, 13). Transductional targeting efforts take advantage of three different methods for capsid remodeling: genetic, noncovalent, and chemical modification. Genetic modification of the coat proteins is the most prevalent method and has been explored at numerous positions on the adenoviral surface; however, due to impact on viral stability and infectivity, most studies focus on the HI loop or C terminus of the fiber protein, the hypervariable region (HVR) within the hexon, and the carboxyl terminus of protein IX (pIX) (4,10,26,35,37). Despite being relatively permissive, genetic alteration of these sites often challenges viral fitness, as evidenced by losses in particle production and infectivity, with such issues determined by the nature and size of modification (12,15,19,22).Noncovalent adenoviral decoration was first demonstrated with chemically modified anti-CAR antibodies. Advantageously, this strategy allows for both detargeting from CARmediated infection and retargeting in a single step (7). Such "molecular bridges" between the vector and the cell-specific receptor consist of two domains; often, the first binds specifically to the primary targeting motif in the knob region, effectively masking it, while the second contains ...

show abstract

“…PEG-modified AdV vectors were conjugated with an anti-HER2/neu monoclonal antibody leading to an enhanced and specific transduction of HER2/neu over-expressed breast cancer cells. Furthermore, a significant reduction of the innate immune response against the vector was accomplished (Jung et al, 2007;Kim et al, 2011). Conjugation of PEG-AdV vectors with an RGD peptide led to a specific α v β 3 integrin vector cell entry.…”

Section: Chemical Modification Of the Adv Capsidmentioning

confidence: 99%

Gene Delivery Systems: Tailoring Vectors to Reach Specific Tissues

Alméciga-Díaz¹,

Cuaspa²,

Barrera³

2011

Non-Viral Gene Therapy

View full text Add to dashboard Cite

Retargeting of adenoviral gene delivery via Herceptin–PEG–adenovirus conjugates to breast cancer cells

Cited by 49 publications

References 31 publications

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

Unnatural Amino Acid Incorporation onto Adenoviral (Ad) Coat Proteins Facilitates Chemoselective Modification and Retargeting of Ad Type 5 Vectors

Gene Delivery Systems: Tailoring Vectors to Reach Specific Tissues

Contact Info

Product

Resources

About